A Phase 1 Multicenter Open-label Study to Evaluate the Safety Tolerability and PK of MEDI0680 (AMP-514) in Subjects with Advanced Malignancies

Study identifier:AMP-514-01

ClinicalTrials.gov identifier:NCT02013804

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0680 (AMP-514) in Subjects with Advanced Malignancies

Medical condition

Advanced Malignancies

Phase

Phase 1

Healthy volunteers

Study drug

MEDI0680 (AMP-514)

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 19 Dec 2013

Primary Completion Date: 18 May 2017

Study Completion Date: 18 May 2017

Study design

Allocation: Non-randomized
Endpoint Classification: Safety
Intervention Model: Sequential Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 May 2019 by MedImmune, LLC

Collaborators

Amplimmune

Inclusion and exclusion criteria

Inclusion Criteria

1. At least 18 years of age at time of study entry
2. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act [HIPAA] in the USA) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations
3. Histologically- or cytologically-confirmed melanoma or clear-cell renal cell carcinoma (RCC) that are
refractory to standard therapy or for which no standard therapy exists
a. Participats must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
b. No more than 3 prior lines of therapy
4. At least 1 measurable lesion per RECIST v1.1; participants whose only measurable lesion is a lymph node will be excluded
5. Eastern Cooperative Oncology Group performance score of 0 or 1
6. For all tumor types, adequate organ and marrow function, as defined below:
a. Hemoglobin >= 9.0 g/dL within first 2 weeks prior to first dose of MEDI0680 (AMP-514)
b. Absolute neutrophil count (ANC) >=1.5 × 10^9/L (1,500/mm^3)
c. Platelet count >= 100 × 10^9/L (100,000/mm^3)
d. Total bilirubin <= 1.5 × ULN except participants with documented Gilbert’s syndrome (> 3 × ULN) or liver metastasis, who must have a baseline total bilirubin <= 3.0 mg/
e. Alanine aminotransferase and AST <= 2.5 × ULN; for participants with hepatic metastases, ALT and AST <= 5 × ULN
f. Serum creatinine <= 1.5 × ULN OR calculated creatinine clearance (CrCl) or 24-hour urine CrCl >= 50 mL/minute
▪ Cockcroft-Gault formula will be used to calculate CrCl; 24-hour urine CrCl will be derived using the measured creatinine clearance formula
7. Prior treatment toxicities must be <= Grade 1

Exclusion Criteria

1. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
2. Receipt of any BRAF inhibitor (in metastatic melanoma), or investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0680 (AMP-514)
3. Prior exposure to immunotherapy, such as, but not limited to, other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies, excluding therapeutic cancer vaccines
4. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI0680 (AMP-514) or still recovering from prior surgery
5. Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
6. Prior allogeneic or autologous bone marrow or organ transplantation that requires use of immunosuppressives
7. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute
Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by MEDI0680 (AMP-514) may be included (eg, hearing loss)
after consultation with the MedImmune medical monitor
8. Active or prior documented autoimmune disease within the past 2 years

Location

Research Site

Detroit, MI, United States, 48201

Location

Research Site

Nashville, TN, United States, 37203

Location

Research Site

Houston, TX, United States, 77030

Location

Research Site

Bronx, NY, United States, 10461

Location

Research Site

Portland, OR, United States, 97213

Location

Research Site

New Haven, CT, United States, 06511

Arms	Assigned Interventions
Experimental: MEDI0680 0.1 mg/kg Q3W Participants will receive intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 0.5 mg/kg Q3W Participants will receive IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 2.5 mg/kg Q3W Participants will receive IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 10 mg/kg Q3W Participants will receive IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 20 mg/kg Q3W Participants will receive IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 10 mg/kg Q2W Participants will receive IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28- day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 20 mg/kg Q2W Participants will receive IV infusion of MEDI0680 20 mg/kg Q2W on Days 1 and 15 of each 28- day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 20 mg/kg QWx2 Participants will receive weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.
Experimental: MEDI0680 20 mg/kg QWx4 Participants will receive weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.	Drug: MEDI0680 (AMP-514) Participants will receive IV infusion of MEDI0680.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted across 6 sites in the United States of America between 19Dec2013 and 18May2017.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 92 participants were screened, of which 58 participants were randomized in the study.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Participant Flow: Overall Study

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
STARTED	5	5	3	6	9	4	18	3	5
COMPLETED	0	0	1	1	0	0	0	0	0
NOT COMPLETED	5	5	2	5	9	4	18	3	5
Study was terminated	0	0	0	0	0	0	1	0	0
Withdrawal by Subject	0	0	0	2	2	0	6	0	3
Lost to Follow-up	0	0	0	0	1	0	0	0	0
Death	5	5	2	3	3	3	8	1	1
Unspecified/Not specified	0	0	0	0	3	1	3	2	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Baseline Measures

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4	Total
Number of Participants [units: Participants]	5	5	3	6	9	4	18	3	5	58
Age Continuous [units: Years] Median ( Full Range )	61.0 (23 to 69)	62.0 (54 to 74)	58.0 (51 to 69)	65.0 (55 to 78)	59.0 (46 to 81)	68.5 (46 to 75)	65.5 (48 to 86)	65.0 (61 to 70)	59.0 (50 to 64)	62.5 (23 to 86)
Sex: Female, Male [units: Participants]
Female	0	1	1	2	1	1	5	0	0	11
Male	5	4	2	4	8	3	13	3	5	47
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	1	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0	0
White	5	5	3	6	9	4	16	3	5	56
More than one race	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	1	0	0	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	0	0	0	0	2	2	1	0	0	5
Not Hispanic or Latino	5	3	3	6	4	2	16	3	4	46
Unknown or Not Reported	0	2	0	0	3	0	1	0	1	7

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: From first dose of study drug (Day 1) until planned dose of subsequent cycle (for MEDI0680 Q3W approximately 21 days; and for MEDI0680 Q2W, MEDI0680 QWx2, and MEDI0680 QWx4 approximately 28 days) ]

Measure Type	Primary
Measure Name	Number of Participants With Dose-limiting Toxicities (DLTs)
Measure Description	The DLT evaluation period is defined as the time period starting with the first dose of MEDI0680 until the planned administration of the second dose of MEDI0680 for Q3W dosing schedule, or the time period starting with the first dose of MEDI0680 until the planned administration of the third dose of MEDI0680 for the Q2W dosing schedule. No DLT was observed and a maximum tolerated dose for MEDI0680 was not reached in this study.
Time Frame	From first dose of study drug (Day 1) until planned dose of subsequent cycle (for MEDI0680 Q3W approximately 21 days; and for MEDI0680 Q2W, MEDI0680 QWx2, and MEDI0680 QWx4 approximately 28 days)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The DLT evaluable population included all participants enrolled in the dose-escalation phase who received the protocol-assigned doses of MEDI0680 (either 1 dose for the Q3W or 2 doses for the Q2W dosing schedule) and completed the safety follow-up through the end of the DLT evaluation period, or experienced a DLT during the DLT evaluation period.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Number of Participants With Dose-limiting Toxicities (DLTs) [units: Participants]	0	0	0	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With Dose-limiting Toxicities (DLTs)

2. Primary Outcome Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are the events between first dose of study drug and up to 90 days end of Study visit or through the first off treatment follow up visit after last dose (approximately 12 months) that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	5	5	3	6	9	4	18	3	5
TESAEs	2	4	0	3	5	1	10	1	2

No statistical analysis provided for Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

3. Primary Outcome Measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs [ Time Frame: From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months) ]

Measure Type	Primary
Measure Name	Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Measure Description	An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis.
Time Frame	From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs [units: Participants]
Anaemia	0	2	1	4	3	1	4	0	2
Iron deficiency anaemia	0	0	0	0	1	0	1	0	0
Leukocytosis	0	0	0	0	0	0	0	0	1
Neutropenia	1	0	0	0	0	0	0	0	0
Anaemia of malignant disease	0	0	0	0	1	0	0	0	0
Lymphadenopathy	0	0	0	0	0	1	0	0	0
Pancytopenia	1	0	0	0	0	0	0	0	0
Lymphocyte count decreased	0	0	1	0	0	0	0	0	0
Hepatic function abnormal	0	0	0	0	0	0	0	0	1
Hyperbilirubinaemia	0	1	0	0	0	0	0	0	0
Alanine aminotransferase increased	0	1	0	0	0	0	1	0	1
Aspartate aminotransferase increased	0	1	0	1	0	0	1	0	0
Lipase increased	0	0	0	0	1	0	2	0	0
Blood alkaline phosphatase increased	0	1	0	0	0	0	0	0	0
Blood creatine phosphokinase increased	0	0	0	0	0	0	1	0	0
Transaminases increased	0	0	0	0	0	0	1	0	1
Hypoalbuminaemia	0	0	0	1	0	0	0	0	0
Blood creatinine increased	0	2	1	1	1	0	1	0	1
Blood urea increased	0	0	0	2	0	0	0	0	1
Proteinuria	0	0	0	0	1	0	2	0	0
Nocturia	0	0	0	1	0	0	1	0	0
Dysuria	0	0	0	0	0	0	1	0	0
Pollakiuria	1	0	0	0	0	0	0	0	0
Hyperthyroidism	0	0	0	0	1	0	1	1	0
Hypothyroidism	0	0	0	1	1	0	1	0	0
Thyroiditis	0	0	0	0	0	0	1	0	0
Hyperparathyroidism	0	0	0	0	0	0	1	0	0
Blood thyroid stimulating hormone increased	0	0	0	1	0	0	0	0	0
Blood thyroid stimulating hormone decreased	0	0	0	0	0	1	0	0	0
Amylase increased	0	0	0	0	1	0	0	0	0
Blood corticotrophin decreased	0	0	1	0	0	0	0	0	0
Blood cortisol decreased	0	0	1	0	0	0	0	0	0
Blood lactate dehydrogenase increased	0	0	0	1	0	0	0	0	0
Blood potassium increased	0	1	0	0	0	0	0	0	0
Hypercalcaemia	0	1	0	0	4	1	0	1	0
Hyperglycaemia	0	1	0	2	0	0	1	0	0
Hyperkalaemia	0	0	1	0	0	1	2	0	1
Hyperphosphataemia	0	0	0	0	0	0	2	0	0
Hyperuricaemia	0	0	1	0	0	0	2	0	0
Hypocalcaemia	0	0	0	0	0	0	1	0	0
Hypokalaemia	0	1	0	1	0	0	0	1	1
Hypomagnesaemia	0	1	0	0	0	0	0	0	0
Hyponatraemia	0	0	0	1	0	0	2	0	0
Hypophosphataemia	0	0	0	0	0	0	0	0	1

No statistical analysis provided for Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

4. Primary Outcome Measure: Number of Participants With Abnormal Electrocardiogram Reported as TEAEs [ Time Frame: From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Electrocardiogram Reported as TEAEs
Measure Description	Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported.
Time Frame	From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Number of Participants With Abnormal Electrocardiogram Reported as TEAEs [units: Participants]
Tachycardia	0	0	0	2	0	0	0	0	0
Atrial fibrillation	0	0	0	1	1	0	0	0	0
Sinus tachycardia	0	1	0	0	0	0	0	0	0
Atrioventricular block first degree	0	0	0	1	0	0	0	0	0
Palpitation	0	0	0	0	1	0	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Electrocardiogram Reported as TEAEs

5. Primary Outcome Measure: Number of Participants With Vital Signs Abnormalities Reported as TEAEs [ Time Frame: From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months) ]

Measure Type	Primary
Measure Name	Number of Participants With Vital Signs Abnormalities Reported as TEAEs
Measure Description	Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported.
Time Frame	From the start of study drug administration (Day 1) throughout the treatment period until either Day 90 end of study visit or through the first off treatment follow up visit after last dose (approximately 12 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Number of Participants With Vital Signs Abnormalities Reported as TEAEs [units: Participants]
Pyrexia	1	1	0	2	0	1	4	1	1
Weight decreased	0	2	0	2	1	1	1	1	0
Hypotension	0	2	0	0	1	0	1	0	1
Hypertension	0	0	0	1	0	1	2	0	0
Weight increased	0	0	0	1	0	1	0	0	0

No statistical analysis provided for Number of Participants With Vital Signs Abnormalities Reported as TEAEs

6. Secondary Outcome Measure: Percentage of Participants With Objective Response [ Time Frame: From Day 1 through end of the study (up to 2 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Objective Response
Measure Description	Objective response (OR) is defined as a complete response (CR) or partial response (PR) that was confirmed no less than 4 weeks (28 days) after the first response criteria was met based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (V1.1) with modification. A confirmed CR is defined as two CRs that were separated by at least 28 days. A confirmed PR is defined as two PRs or an unconfirmed PR and an unconfirmed CR that were separated by at least 28 days. A CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. A SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study.
Time Frame	From Day 1 through end of the study (up to 2 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Percentage of Participants With Objective Response [units: Percentage of participants] Number (95% Confidence Interval)	0 (0.0 to 52.2)	0 (0.0 to 52.2)	0 (0.0 to 70.8)	16.7 (0.4 to 64.1)	33.3 (7.5 to 70.1)	25.0 (0.6 to 80.6)	16.7 (3.6 to 41.4)	0 (0.0 to 70.8)	0 (0.0 to 52.2)

No statistical analysis provided for Percentage of Participants With Objective Response

7. Secondary Outcome Measure: Percentage of Participants With Disease Control [ Time Frame: From Day 1 through end of the study (up to 2 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Disease Control
Measure Description	Disease control is defined as confirmed CR or PR, or stable disease (SD) (participants achieving SD were included in the disease control) based on RECIST version 1.1 with modification.
Time Frame	From Day 1 through end of the study (up to 2 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Percentage of Participants With Disease Control [units: Percentage of participants] Number (95% Confidence Interval)
CR+PR+SD >=8 weeks	0 (0.0 to 52.2)	0 (0.0 to 52.2)	33.3 (0.8 to 90.6)	50.0 (11.8 to 88.2)	55.6 (21.2 to 86.3)	50.0 (6.8 to 93.2)	44.4 (21.5 to 69.2)	66.7 (9.4 to 99.2)	60.0 (14.7 to 94.7)
CR+PR+SD >=24 weeks	0 (0.0 to 52.2)	0 (0.0 to 52.2)	33.3 (0.8 to 90.6)	33.3 (4.3 to 77.7)	44.4 (13.7 to 78.8)	25.0 (0.6 to 80.6)	27.8 (9.7 to 53.5)	66.7 (9.4 to 99.2)	40.0 (5.3 to 85.3)

No statistical analysis provided for Percentage of Participants With Disease Control

8. Secondary Outcome Measure: Duration of Response [ Time Frame: From Day 1 through end of the study (up to 2 years) ]

Measure Type	Secondary
Measure Name	Duration of Response
Measure Description	Duration of response is defined as the duration from the first documentation of objective response (OR) to the first documented disease progression or death due to any cause, whichever occurred first. For participants who are alive and progression-free at the time of data cut-off for analysis, duration of response was to be censored at the last tumor assessment date.
Time Frame	From Day 1 through end of the study (up to 2 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. Duration of response was estimated for the subgroup of participants with an OR.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Duration of Response [units: Weeks] Median (Full Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]	110.7 (110.7 to 110.7)	NA (9.1 to 79.1) ^[1]	NA (84.4 to 84.4) ^[1]	24.4 (17.1 to 24.4)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]

No statistical analysis provided for Duration of Response

9. Secondary Outcome Measure: Progression-free Survival (PFS) [ Time Frame: From Day 1 through end of the study (up to 2 years) ]

Measure Type	Secondary
Measure Name	Progression-free Survival (PFS)
Measure Description	Progression-free survival is measured from the start of treatment with study drug until the documentation of disease progression or death due to any cause, whichever occurred first. For participants who are alive and progression-free at the time of data cut-off for analysis, PFS was to be censored at the last tumor assessment date.
Time Frame	From Day 1 through end of the study (up to 2 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Progression-free Survival (PFS) [units: Months] Median (Full Range)	1.4 (0.0 to 2.8)	2.8 (2.5 to 4.2)	2.7 (1.9 to 7.0)	6.9 (0.0 to 27.4)	12.0 (1.2 to 22.3)	2.8 (1.6 to 23.1)	3.6 (1.4 to 8.2)	5.7 (1.9 to 8.0)	3.3 (1.8 to 7.3)

No statistical analysis provided for Progression-free Survival (PFS)

10. Secondary Outcome Measure: Overall Survival [ Time Frame: From Day 1 through end of the study (up to 2 years) ]

Measure Type	Secondary
Measure Name	Overall Survival
Measure Description	The overall survival is determined as the time from the start of treatment with study drug until death due to any cause. For participants who are alive at the time of data cut-off for analysis, overall survival was to be censored at the last date when participants were known to be alive.
Time Frame	From Day 1 through end of the study (up to 2 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Overall Survival [units: Months] Median (Full Range)	4.9 (0.4 to 8.5)	5.2 (2.7 to 6.6)	28.3 (14.3 to 28.3)	31.1 (2.7 to 31.1)	NA (1.2 to 32.3) ^[1]	6.4 (3.8 to 31.6)	18.4 (1.4 to 30.1)	NA (10.2 to 24.4) ^[1]	NA (3.7 to 23.8) ^[1]

No statistical analysis provided for Overall Survival

11. Secondary Outcome Measure: Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680 [ Time Frame: Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680
Measure Description	The area under the serum concentration-time curve during dosing interval after the first dose of MEDI0680 was reported.
Time Frame	Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680 [units: μg*day/mL] Geometric Mean (Geometric Coefficient of Variation)	22.0 (17.4%)	117 (13.6%)	742 (24.5%)	3168 (27.3%)	3827 (64.7%)	2038 (16.6%)	3285 (37.3%)	2156 (26.9%)	2825 (23.2%)

No statistical analysis provided for Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680

12. Secondary Outcome Measure: Dose Normalized Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680 [ Time Frame: Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2 ]

Measure Type	Secondary
Measure Name	Dose Normalized Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680
Measure Description	The dose normalized area under the serum concentration-time curve during dosing interval after the first dose of MEDI0680 was reported.
Time Frame	Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Dose Normalized Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680 [units: μg*day/mL/mg] Geometric Mean (Geometric Coefficient of Variation)	3.17 (19.9%)	2.60 (27.9%)	3.15 (37.1%)	3.75 (32.2%)	2.3 (50.9%)	2.79 (10.6%)	2.057 (31.4%)	1.11 (14.3%)	1.22 (26.0%)

No statistical analysis provided for Dose Normalized Area Under the Serum Concentration-time Curve During Dosing Interval After the First Dose of MEDI0680

13. Secondary Outcome Measure: Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680 [ Time Frame: Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2 ]

Measure Type	Secondary
Measure Name	Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680
Measure Description	The Cmax after the first dose of MEDI0680 was reported.
Time Frame	Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680 [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)	3.06 (17.1%)	13.4 (10.1%)	85.2 (7.74%)	348 (26.1%)	587 (40.5%)	311 (30.2%)	544 (35.2%)	524 (42.5%)	750 (15.3%)

No statistical analysis provided for Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680

14. Secondary Outcome Measure: Dose Normalized Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680 [ Time Frame: Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2 ]

Measure Type	Secondary
Measure Name	Dose Normalized Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680
Measure Description	The dose normalized Cmax after the first dose of MEDI0680 was reported.
Time Frame	Cycle 1: Day 1 (predose; end of infusion, 1, and 4 hours postdose), Days 2, 4, 8, 15, and pre-dose of cycle 2
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Dose Normalized Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680 [units: μg/mL/mg] Geometric Mean (Geometric Coefficient of Variation)	0.42 (17.1%)	0.31 (32.4%)	0.362 (26.1%)	0.422 (22.2%)	0.353 (36.3%)	0.426 (10.04%)	0.346 (34.5%)	0.269 (29.23%)	0.362 (32.6%)

No statistical analysis provided for Dose Normalized Maximum Observed Serum Concentration (Cmax) After the First Dose of MEDI0680

15. Secondary Outcome Measure: Number of Participants With Positive Anti-drug Antibodies to MEDI0680 [ Time Frame: Day 1 (predose), Days 15, 29, 43, 57, 71, 85, 99, 113, every 2 weeks until end of treatment (EOT) (14 days after last dose of study drug), EOT, and 30 days post EOT (up to 3 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive Anti-drug Antibodies to MEDI0680
Measure Description	Participants with positive antibodies to MEDI0680 are reported.
Time Frame	Day 1 (predose), Days 15, 29, 43, 57, 71, 85, 99, 113, every 2 weeks until end of treatment (EOT) (14 days after last dose of study drug), EOT, and 30 days post EOT (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Measured Values

	MEDI0680 0.1 mg/kg Q3W	MEDI0680 0.5 mg/kg Q3W	MEDI0680 2.5 mg/kg Q3W	MEDI0680 10 mg/kg Q3W	MEDI0680 20 mg/kg Q3W	MEDI0680 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg QWx2	MEDI0680 20 mg/kg QWx4
Number of Participants Analyzed [units:participants]	5	5	3	6	9	4	18	3	5
Number of Participants With Positive Anti-drug Antibodies to MEDI0680 [units: Participants]	2	1	2	1	1	0	0	1	0

No statistical analysis provided for Number of Participants With Positive Anti-drug Antibodies to MEDI0680

Serious Adverse Events

Time Frame	From the start of study drug administration (Day 1), throughout the treatment period until either Day 90 End of Study visit or through the first off treatment follow up visit after last dose (approximately 12 months)
Additional Description	No text entered.

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Serious Adverse Events

MEDI0680 0.1 mg/kg Q3W

MEDI0680 0.5 mg/kg Q3W

MEDI0680 2.5 mg/kg Q3W

MEDI0680 10 mg/kg Q3W

MEDI0680 20 mg/kg Q3W

MEDI0680 10 mg/kg Q2W

MEDI0680 20 mg/kg Q2W

MEDI0680 20 mg/kg QWx2

MEDI0680 20 mg/kg QWx4

Total, serious adverse events

# participants affected / at risk

2/5 (40.00%)

4/5 (80.00%)

0/3 (0.00%)

3/6 (50.00%)

5/9 (55.56%)

1/4 (25.00%)

10/18 (55.56%)

1/3 (33.33%)

2/5 (40.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Cardiac disorders

Acute coronary syndrome¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Myocarditis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Gastrointestinal haemorrhage¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Intestinal obstruction¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Obstruction gastric¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Disease progression¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

3/18 (16.67%)

1/3 (33.33%)

0/5 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Flank pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myositis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cancer metastatic¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Aphasia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Haemorrhage intracranial¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Myasthenia gravis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Spinal cord compression¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Dysuria¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

2/5 (40.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Superior vena cava syndrome¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.1

Other Adverse Events

Time Frame	From the start of study drug administration (Day 1), throughout the treatment period until either Day 90 End of Study visit or through the first off treatment follow up visit after last dose (approximately 12 months)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
MEDI0680 0.1 mg/kg Q3W	Participants received intravenous (IV) infusion of MEDI0680 0.1 milligram / kilogram once in every three weeks (Q3W) on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 0.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 0.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 2.5 mg/kg Q3W	Participants received IV infusion of MEDI0680 2.5 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q3W	Participants received IV infusion of MEDI0680 10 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q3W	Participants received IV infusion of MEDI0680 20 mg/kg Q3W on Day 1 of each 21-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 10 mg/kg Q2W	Participants received IV infusion of MEDI0680 10 mg/kg once every two weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg Q2W	Participants received IV infusion of MEDI0680 20 mg/kg Q2W on on Days 1 and 15 of each 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx2	Participants received weekly 2 doses of IV infusion of MEDI0680 20 mg/kg QWx2 (Days 1 and 8) in Cycle 1 and followed by Q2W dosing from Day 15 for a 28-day treatment cycle for 12 months or confirmed progressive disease.
MEDI0680 20 mg/kg QWx4	Participants received weekly 4 doses of IV infusion of MEDI0680 20 mg/kg QWx4 (Days 1, 8, 15, and 22) in Cycle 1 and followed by Q2W dosing from Day 29 for a 28-day treatment cycle for 12 months or confirmed progressive disease.

Other Adverse Events

MEDI0680 0.1 mg/kg Q3W

MEDI0680 0.5 mg/kg Q3W

MEDI0680 2.5 mg/kg Q3W

MEDI0680 10 mg/kg Q3W

MEDI0680 20 mg/kg Q3W

MEDI0680 10 mg/kg Q2W

MEDI0680 20 mg/kg Q2W

MEDI0680 20 mg/kg QWx2

MEDI0680 20 mg/kg QWx4

Total, other (not including serious) adverse events

# participants affected / at risk

5/5 (100.00%)

3/3 (100.00%)

6/6 (100.00%)

9/9 (100.00%)

4/4 (100.00%)

17/18 (94.44%)

3/3 (100.00%)

5/5 (100.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

1/3 (33.33%)

4/6 (66.67%)

3/9 (33.33%)

1/4 (25.00%)

4/18 (22.22%)

0/3 (0.00%)

2/5 (40.00%)

# events

Blood and lymphatic system disorders

Anaemia of malignant disease¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Blood and lymphatic system disorders

Iron deficiency anaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Blood and lymphatic system disorders

Leukocytosis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Blood and lymphatic system disorders

Lymphadenopathy¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Blood and lymphatic system disorders

Pancytopenia¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Atrioventricular block first degree¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Tachycardia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Endocrine disorders

Adrenal insufficiency¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Endocrine disorders

Hyperparathyroidism¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Endocrine disorders

Hyperthyroidism¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

1/3 (33.33%)

0/5 (0.00%)

# events

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Endocrine disorders

Thyroiditis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Dry eye¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Eye disorders

Eye swelling¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Eyelid margin crusting¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Eyelid ptosis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Iridocyclitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Eye disorders

Vision blurred¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Eye disorders

Visual impairment¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Vitreous floaters¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

1/3 (33.33%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain lower¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal tenderness¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

1/5 (20.00%)

3/5 (60.00%)

1/3 (33.33%)

0/6 (0.00%)

2/9 (22.22%)

0/4 (0.00%)

5/18 (27.78%)

0/3 (0.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

3/3 (100.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Dry mouth¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Faeces discoloured¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

2/18 (11.11%)

0/3 (0.00%)

2/5 (40.00%)

# events

Gastrointestinal disorders

Glossodynia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Hypoaesthesia oral¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/5 (20.00%)

2/5 (40.00%)

0/3 (0.00%)

3/6 (50.00%)

1/9 (11.11%)

1/4 (25.00%)

4/18 (22.22%)

1/3 (33.33%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Oral pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Paraesthesia oral¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Pigmentation buccal¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Swollen tongue¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

4/18 (22.22%)

1/3 (33.33%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

1/5 (20.00%)

2/5 (40.00%)

0/3 (0.00%)

0/6 (0.00%)

2/9 (22.22%)

1/4 (25.00%)

4/18 (22.22%)

2/3 (66.67%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

3/18 (16.67%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Chills¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Early satiety¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

1/3 (33.33%)

3/6 (50.00%)

4/9 (44.44%)

2/4 (50.00%)

7/18 (38.89%)

1/3 (33.33%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Gait disturbance¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

General physical health deterioration¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

General disorders and administration site conditions

Hypothermia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Ill-defined disorder¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

2/9 (22.22%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Injection site haemorrhage¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Mucosal discolouration¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

1/5 (20.00%)

2/5 (40.00%)

0/3 (0.00%)

0/6 (0.00%)

2/9 (22.22%)

0/4 (0.00%)

3/18 (16.67%)

1/3 (33.33%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

1/4 (25.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Peripheral swelling¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

1/4 (25.00%)

4/18 (22.22%)

1/3 (33.33%)

1/5 (20.00%)

# events

General disorders and administration site conditions

Tenderness¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Hepatobiliary disorders

Autoimmune hepatitis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Hepatobiliary disorders

Bile duct stenosis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Hepatobiliary disorders

Hyperbilirubinaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Immune system disorders

Seasonal allergy¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Atypical pneumonia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Candida infection¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Conjunctivitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Cystitis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Oral herpes¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Postoperative wound infection¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

2/9 (22.22%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

0/3 (0.00%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Vulvovaginal mycotic infection¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Injury, poisoning and procedural complications

Exposure to toxic agent¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

1/3 (33.33%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Injury, poisoning and procedural complications

Incision site pruritus¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Joint injury¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Postoperative ileus¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Procedural pain¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Skin abrasion¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Injury, poisoning and procedural complications

Subdural haematoma¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Investigations

Amylase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood corticotrophin decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood cortisol decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood creatine phosphokinase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

1/3 (33.33%)

1/6 (16.67%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Investigations

Blood lactate dehydrogenase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood potassium increased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood thyroid stimulating hormone decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood thyroid stimulating hormone increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood urea increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Investigations

Breath sounds abnormal¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Cardiac murmur¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Investigations

Electrocardiogram st segment depression¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Lipase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Lymphocyte count decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Investigations

Transaminases increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

0/3 (0.00%)

2/6 (33.33%)

1/9 (11.11%)

1/4 (25.00%)

1/18 (5.56%)

1/3 (33.33%)

0/5 (0.00%)

# events

Investigations

Weight increased¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Cachexia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

2/5 (40.00%)

2/3 (66.67%)

3/6 (50.00%)

1/9 (11.11%)

2/4 (50.00%)

4/18 (22.22%)

1/3 (33.33%)

2/5 (40.00%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

0/3 (0.00%)

2/6 (33.33%)

2/9 (22.22%)

1/4 (25.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Fluid overload¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Gout¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

4/9 (44.44%)

1/4 (25.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

2/18 (11.11%)

0/3 (0.00%)

1/5 (20.00%)

# events

Metabolism and nutrition disorders

Hyperphosphataemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyperuricaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

1/5 (20.00%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

3/9 (33.33%)

0/4 (0.00%)

4/18 (22.22%)

2/3 (66.67%)

2/5 (40.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

1/4 (25.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Groin pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

3/18 (16.67%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal discomfort¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

1/5 (20.00%)

# events

Musculoskeletal and connective tissue disorders

Myositis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

3/18 (16.67%)

0/3 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Tendonitis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cancer pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Melanocytic naevus¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Aphasia¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Brain oedema¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Burning sensation¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

Nervous system disorders

Dizziness postural¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

3/18 (16.67%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Lacunar infarction¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Lethargy¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Myasthenia gravis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

2/9 (22.22%)

0/4 (0.00%)

3/18 (16.67%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Peripheral sensory neuropathy¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Nervous system disorders

Presyncope¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Visual field defect¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Psychiatric disorders

Agitation¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

1/9 (11.11%)

0/4 (0.00%)

5/18 (27.78%)

1/3 (33.33%)

0/5 (0.00%)

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

3/9 (33.33%)

1/4 (25.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

1/3 (33.33%)

1/5 (20.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

1/5 (20.00%)

1/3 (33.33%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

1/3 (33.33%)

1/5 (20.00%)

# events

Psychiatric disorders

Mental status changes¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Renal and urinary disorders

Incontinence¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Nocturia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Proteinuria¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Stress urinary incontinence¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Urethral pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Urinary hesitation¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Urinary incontinence¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Breast swelling¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Breast tenderness¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Erectile dysfunction¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Gynaecomastia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Pelvic pain¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Prostatitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Allergic bronchitis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Atelectasis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

1/3 (33.33%)

0/6 (0.00%)

1/9 (11.11%)

1/4 (25.00%)

3/18 (16.67%)

3/3 (100.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

2/5 (40.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹,^†

# participants affected / at risk

1/5 (20.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

7/18 (38.89%)

1/3 (33.33%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

1/9 (11.11%)

0/4 (0.00%)

4/18 (22.22%)

1/3 (33.33%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory distress¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinitis allergic¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sinus congestion¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Wheezing¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Cold sweat¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

2/18 (11.11%)

0/3 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Facial wasting¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Hyperhidrosis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Lichenoid keratosis¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pain of skin¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Papule¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Photosensitivity reaction¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

3/18 (16.67%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus generalised¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

0/3 (0.00%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Rash erythematous¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

1/3 (33.33%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash macular¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/9 (11.11%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash pruritic¹,^†

# participants affected / at risk

0/5 (0.00%)

1/3 (33.33%)

2/6 (33.33%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Skin discolouration¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Skin hyperpigmentation¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

1/4 (25.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Skin mass¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Flushing¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

0/18 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/5 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/9 (0.00%)

1/4 (25.00%)

2/18 (11.11%)

0/3 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/6 (0.00%)

0/9 (0.00%)

0/4 (0.00%)

1/18 (5.56%)

0/3 (0.00%)

1/5 (20.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The PK parameters clearance (CL), volume of distribution (Vd), and terminal elimination half-life (t1/2) were not reported from noncompartmental analysis (NCA) due to small sample size and lower accuracy.