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.