Study of MEDI4736 monotherapy and in combination with Tremelimumab versus Standard of Care Therapy in patients with head and neck cancer - EAGLE

Study identifier:D4193C00002

ClinicalTrials.gov identifier:NCT02369874

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination with Tremelimumab Versus Standard of Care Therapy in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Medical condition

Recurrent or metastatic PD-L1-positive or -negative squamous cell carcinoma of the head and neck SCCHN

Phase

Phase 3

Healthy volunteers

Study drug

MEDI4736, MEDI4736 + Tremelimumab, Standard of Care

Sex

All

Actual Enrollment

736

Study type

Interventional

Age

18 Years - 96 Years

Date

Study Start Date: 09 Sept 2015

Primary Completion Date: 10 Sept 2018

Study Completion Date: 13 Nov 2020

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2021 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Age ≥18 years; - Written informed consent obtained from the patient/legal representative; - Histologically or cytologically confirmed recurrent or metastatic SCCHN; - Tumor progression or recurrence during or after only one palliative systemic treatment regimen for recurrent or metastatic disease that must have contained a platinum agent OR progression within 6 months of the last dose of platinum given as part of multimodality therapy with curative intent; - Confirmed PD-L1–positive or -negative SCCHN by the Ventana PD-L1 SP263 IHC assay; - WHO/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; At least 1 measurable lesion, - Not previously irradiated; - No prior exposure to immune-mediated therapy; - Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion Criteria

- Histologically or cytologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck; - Received more than 1 palliative systemic regimen for recurrent or metastatic disease; -Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment; - Receipt of any investigational anticancer therapy within 28 days or 5 half-lives; - Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment; - Major surgical procedure within 28 days prior to the first dose of Investigational Product; - Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion; - Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product; - History of allogeneic organ transplantation; - Active or prior documented autoimmune or inflammatory disorders; - Uncontrolled intercurrent illness; - Patients with a history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis; - Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction; - History of active primary immunodeficiency; - Active tuberculosis; - Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV); - Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product; - Pregnant or breast-feeding female patients; - Known allergy or hypersensitivity to Investigational Product

Location

Research Site

CABA, Argentina, C1426ANZ

Location

Research Site

San Miguel de Tucuman, Argentina, T4000IAK

Location

Research Site

Namur, Belgium, 5000

Location

Research Site

Bruxelles, Belgium, 1200

Location

Research Site

Leuven, Belgium, 3000

Location

Research Site

Brussels, Belgium, 1090

Location

Research Site

Charleroi, Belgium, 6000

Location

Research Site

Kortrijk, Belgium, 8500

Arms	Assigned Interventions
Experimental: MEDI4736 MEDI4736 monotherapy	Drug: MEDI4736 MEDI4736 Monotherapy
Experimental: MEDI4736 + Tremelimumab MEDI4736 + tremelimumab combination therapy	Drug: MEDI4736 + Tremelimumab MEDI4736 + Tremelimumab combination therapy
Active Comparator: Standard of Care Standard of Care	Drug: Standard of Care Standard of Care

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Participant Flow: Overall Study

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
STARTED	247	240	249
Received Treatment	246	237	240
COMPLETED	203	183	188
NOT COMPLETED	44	57	61
Lost to Follow-up	2	2	2
Withdrawal by Subject	7	9	27
Miscellaneous	1	1	0
On Treatment/Off Study	34	45	32

Baseline Characteristics

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

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Baseline Measures

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)	Total
Number of Participants [units: Participants]	247	240	249	736
Age Continuous [units: Years] Mean ± Standard Deviation	59.9 ± 9.14	59.0 ± 10.07	59.5 ± 10.37	59.4 ± 9.86
Age, Customized [units: Participants]
< 65 Years	174	169	171	514
>= 65 - < 75 Years	63	56	64	183
>= 75 Years	10	15	14	39
Sex: Female, Male [units: ]
Female	38	38	42	118
Male	209	202	207	618
Race/Ethnicity, Customized [units: Participants]
Asian	33	35	45	113
Black Or African American	1	0	3	4
Other	4	5	3	12
White	204	198	189	591
Unknown or Not Reported	5	2	9	16
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	16	15	13	44
Not Hispanic or Latino	226	223	229	678
Unknown or Not Reported	5	2	7	14

Outcome Measures

1. Primary Outcome Measure: Overall survival (OS) [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Primary
Measure Name	Overall survival (OS)
Measure Description	OS is defined as the time from the date of randomization until death due to any cause. OS was analyzed for the full analysis set, regardless of programmed death-ligand 1 (PD-L1) status.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
Full analysis set - inclusive of all randomized participants.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	247	240	249
Overall survival (OS) [units: Months] Median (95% Confidence Interval)	6.5 (5.5 to 8.2)	7.6 (6.1 to 9.8)	8.3 (7.3 to 9.2)

Statistical Analysis 1 for Overall survival (OS)

Groups^[1]	Durvalumab + Tremelimumab, Standard of Care (SoC)
Method^[3]	Log Rank
P-Value^[4]	0.7624
Hazard Ratio (HR)^[5]	1.04
95% Confidence Interval	( 0.85 to 1.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Overall survival (OS)

Groups^[1]	Durvalumab, Standard of Care (SoC)
Method^[3]	Log Rank
P-Value^[4]	0.1993
Hazard Ratio (HR)^[5]	0.88
95% Confidence Interval	( 0.72 to 1.08 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Overall survival (OS) in PD-L1 negative participants [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Overall survival (OS) in PD-L1 negative participants
Measure Description	OS is defined as the time from the date of randomization until death due to any cause. PD-L1 negative was defined as <25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
PD-L1-negative analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-negative as defined by the Ventana PD-L1 SP263 IHC assay.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	175	172	177
Overall survival (OS) in PD-L1 negative participants [units: Months] Median (95% Confidence Interval)	7.8 (5.9 to 10.3)	7.6 (6.2 to 9.5)	8.0 (6.7 to 8.9)

Statistical Analysis 1 for Overall survival (OS) in PD-L1 negative participants

Groups^[1]	Durvalumab + Tremelimumab, Standard of Care (SoC)
Method^[3]	Log Rank
P-Value^[4]	0.4590
Hazard Ratio (HR)^[5]	0.92
95% Confidence Interval	( 0.73 to 1.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Overall survival (OS) in PD-L1 negative participants

Groups^[1]	Durvalumab + Tremelimumab, Durvalumab
Hazard Ratio (HR)^[5]	1.08
95% Confidence Interval	( 0.85 to 1.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Overall survival (OS) in PD-L1 positive participants [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Overall survival (OS) in PD-L1 positive participants
Measure Description	OS is defined as the time from the date of randomization until death due to any cause. PD-L1 positive was defined as ≥25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
PD-L1-positive analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-positive as defined by the Ventana PD-L1 SP263 IHC assay.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	72	68	72
Overall survival (OS) in PD-L1 positive participants [units: Months] Median (95% Confidence Interval)	4.8 (3.3 to 6.4)	9.8 (4.3 to 14.1)	9.0 (6.8 to 9.2)

Statistical Analysis 1 for Overall survival (OS) in PD-L1 positive participants

Groups^[1]	Durvalumab, Standard of Care (SoC)
Hazard Ratio (HR)^[5]	0.93
95% Confidence Interval	( 0.63 to 1.39 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Progression free survival (PFS) [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Progression free survival (PFS)
Measure Description	PFS was defined as the time from the date of randomization until the date of objective disease progression or death based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
Full analysis set - inclusive of all randomized participants.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	247	240	249
Progression free survival (PFS) [units: Months] Median (95% Confidence Interval)	2.0 (1.9 to 2.3)	2.1 (1.9 to 3.0)	3.7 (3.1 to 3.7)

Statistical Analysis 1 for Progression free survival (PFS)

Groups^[1]	Durvalumab + Tremelimumab, Standard of Care (SoC)
Hazard Ratio (HR)^[5]	1.09
95% Confidence Interval	( 0.90 to 1.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Progression free survival (PFS)

Groups^[1]	Durvalumab, Standard of Care (SoC)
Hazard Ratio (HR)^[5]	1.02
95% Confidence Interval	( 0.84 to 1.25 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Objective response rate (ORR) [ Time Frame: Assessed at randomization and every 8 weeks thereafter ]

Measure Type	Secondary
Measure Name	Objective response rate (ORR)
Measure Description	The percentage of participants who experienced an objective response (complete response [CR] or partial response [PR]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Time Frame	Assessed at randomization and every 8 weeks thereafter
Safety Issue?

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.
Full analysis set - inclusive of all randomized participants.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	247	240	249
Objective response rate (ORR) [units: Percentage of participants] Number (95% Confidence Interval)	18.2 (13.6 to 23.6)	17.9 (13.3 to 23.4)	17.3 (12.8 to 22.5)

Statistical Analysis 1 for Objective response rate (ORR)

Groups^[1]	Durvalumab + Tremelimumab, Standard of Care (SoC)
Odds Ratio (OR)^[5]	1.07
95% Confidence Interval	( 0.67 to 1.70 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Objective response rate (ORR)

Groups^[1]	Durvalumab, Standard of Care (SoC)
Odds Ratio (OR)^[5]	1.05
95% Confidence Interval	( 0.66 to 1.68 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Duration of response (DoR) [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Duration of response (DoR)
Measure Description	Median DoR, in months, based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A complete response was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A partial response was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
Full analysis set, participants with objective response - inclusive of all randomized participants with an objective response (RECIST 1.1).

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	45	43	43
Duration of response (DoR) [units: Months] Median (Inter-Quartile Range)	7.4 (2.8 to N/A) ^[1]	12.9 (5.6 to N/A) ^[1]	3.7 (1.9 to 5.5)

No statistical analysis provided for Duration of response (DoR)

7. Secondary Outcome Measure: Disease control rate (DCR) [ Time Frame: Baseline up to 6 months; baseline up to 12 months ]

Measure Type	Secondary
Measure Name	Disease control rate (DCR)
Measure Description	6 Months: The percentage of participants who had a best objective response of complete response (CR) or partial response (PR) in the first 6 months or had demonstrated stable disease (SD) for a minimum interval of 24 weeks following randomization. 12 Months: The percentage of participants who had a best objective response of CR or PR within 12 months or had demonstrated SD for a minimum interval of 48 weeks following randomization. Objective response was based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.
Time Frame	Baseline up to 6 months; baseline up to 12 months
Safety Issue?

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.
Full analysis set - inclusive of all randomized participants.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	247	240	249
Disease control rate (DCR) [units: Percentage of participants]
6 Months	25.1	24.2	24.9
12 Months	20.6	18.8	18.9

Statistical Analysis 1 for Disease control rate (DCR)

Groups^[1]	Durvalumab + Tremelimumab, Standard of Care (SoC)
Odds Ratio (OR)^[5]	1.01
95% Confidence Interval	( 0.67 to 1.52 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	6 Month analysis
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Disease control rate (DCR)

Groups^[1]	Durvalumab, Standard of Care (SoC)
Odds Ratio (OR)^[5]	0.96
95% Confidence Interval	( 0.64 to 1.46 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	6 Month analysis
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Disease control rate (DCR)

Groups^[1]	Durvalumab + Tremelimumab, Standard of Care (SoC)
Odds Ratio (OR)^[5]	1.12
95% Confidence Interval	( 0.72 to 1.75 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	12 Month analysis
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Disease control rate (DCR)

Groups^[1]	Durvalumab, Standard of Care (SoC)
Odds Ratio (OR)^[5]	1.00
95% Confidence Interval	( 0.63 to 1.57 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	12 Month analysis
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Percentage of participants alive and progression free (APF) [ Time Frame: Baseline up to 6 months; baseline up to 12 months ]

Measure Type	Secondary
Measure Name	Percentage of participants alive and progression free (APF)
Measure Description	APF is defined as the percentage of participants who are alive and progression free at 6 months and 12 months after randomization. Estimates of progression free survival were based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Baseline up to 6 months; baseline up to 12 months
Safety Issue?

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.
Full analysis set - inclusive of all randomized participants.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	247	240	249
Percentage of participants alive and progression free (APF) [units: Percentage of participants] Number (95% Confidence Interval)
6 Months	22.5 (17.4 to 28.0)	25.1 (19.7 to 30.9)	23.3 (17.8 to 29.3)
12 Months	11.0 (7.4 to 15.5)	14.4 (10.1 to 19.5)	5.7 (2.8 to 10.2)

No statistical analysis provided for Percentage of participants alive and progression free (APF)

9. Secondary Outcome Measure: Percentage of participants alive [ Time Frame: 12, 18 and 24 months ]

Measure Type	Secondary
Measure Name	Percentage of participants alive
Measure Description	Percentage of participants alive at 12, 18 and 24 months using a Kaplan Meier estimate.
Time Frame	12, 18 and 24 months
Safety Issue?

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.
Full analysis set - inclusive of all randomized participants.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	247	240	249
Percentage of participants alive [units: Percentage of participants] Number (95% Confidence Interval)
12 Months	30.4 (24.7 to 36.3)	37.0 (30.9 to 43.1)	30.5 (24.7 to 36.4)
18 Months	21.0 (15.9 to 26.5)	25.4 (19.9 to 31.3)	17.8 (13.1 to 23.2)
24 Months	13.3 (8.9 to 18.6)	18.4 (13.3 to 24.1)	10.3 (5.7 to 16.5)

No statistical analysis provided for Percentage of participants alive

10. Secondary Outcome Measure: Progression free survival (PFS) in PD-L1 negative participants [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Progression free survival (PFS) in PD-L1 negative participants
Measure Description	Number of participants with confirmed objective disease progression (PD) at the time of the participant's last evaluable response evaluation criteria in solid tumors 1.1 (RECIST1.1) assessment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD-L1 negative was defined as <25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
PD-L1-negative analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-negative as defined by the Ventana PD-L1 SP263 IHC assay.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	175	172	177
Progression free survival (PFS) in PD-L1 negative participants [units: Participants]	154	151	144

Statistical Analysis 1 for Progression free survival (PFS) in PD-L1 negative participants

Groups^[1]	Durvalumab + Tremelimumab, Durvalumab
Hazard Ratio (HR)^[5]	0.96
95% Confidence Interval	( 0.76 to 1.21 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

11. Secondary Outcome Measure: Objective response rate (ORR) in PD-L1 negative participants [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Objective response rate (ORR) in PD-L1 negative participants
Measure Description	The percentage of PD-L1 negative participants who experienced an objective response (complete response [CR] or partial response [PR]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. PD-L1 negative was defined as <25% of tumor cells with membrane staining for PD-L1 at any intensity.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
PD-L1-negative analysis set - inclusive of all randomized participants whose PD-L1 status is PD-L1-negative as defined by the Ventana PD-L1 SP263 IHC assay.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	175	172	177
Objective response rate (ORR) in PD-L1 negative participants [units: Percentage of participants] Number (95% Confidence Interval)	17.7 (12.4 to 24.2)	14.0 (9.1 to 20.0)	15.3 (10.3 to 21.4)

Statistical Analysis 1 for Objective response rate (ORR) in PD-L1 negative participants

Groups^[1]	Durvalumab + Tremelimumab, Durvalumab
Odds Ratio (OR)^[5]	1.33
95% Confidence Interval	( 0.74 to 2.39 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

12. Secondary Outcome Measure: Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire, version 3 (EORTC QLQ-C30) [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire, version 3 (EORTC QLQ-C30)
Measure Description	The EORTC QLQ-C30 consists of 30 questions that can be combined to produce functional scales (e.g. physical), symptom scales (e.g. fatigue), and a global measure of health status. Each of the scales are measured from 0 to 100. Deterioration was defined as a 10-point decrease from baseline in a functioning or global health status/ quality of life score or a 10-point increase from baseline in a symptom score.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
All randomized patients who provided questionnaire data

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	227	226	227
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire, version 3 (EORTC QLQ-C30) [units: Months] Median (95% Confidence Interval)
Function - Physical	2.0 (1.9 to 3.2)	2.2 (1.9 to 3.5)	3.7 (2.3 to 4.6)
Symptom - Fatigue	1.8 (1.3 to 1.9)	1.4 (1.0 to 1.9)	1.9 (1.6 to 2.6)
Global health status/QoL	1.9 (1.8 to 2.7)	2.8 (1.9 to 3.8)	3.5 (2.9 to 4.0)

No statistical analysis provided for Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire, version 3 (EORTC QLQ-C30)

13. Secondary Outcome Measure: Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item head and neck quality of life questionnaire (EORTC QLQ-H&N35) [ Time Frame: September 2015 to September 2018 (36 months) ]

Measure Type	Secondary
Measure Name	Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item head and neck quality of life questionnaire (EORTC QLQ-H&N35)
Measure Description	The EORTC QLQ-H&N35 comprises of 35 questions to assess head and neck cancer symptoms (e.g. pain, swallowing). Deterioration was defined as a 10-point increase from baseline in the symptom score.
Time Frame	September 2015 to September 2018 (36 months)
Safety Issue?

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.
All randomized patients who provided questionnaire data

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	223	220	221
Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item head and neck quality of life questionnaire (EORTC QLQ-H&N35) [units: Months] Median (95% Confidence Interval)
Pain (Mouth/ Throat)	2.9 (2.4 to 3.8)	2.8 (2.6 to 3.7)	3.4 (2.7 to 4.0)
Swallowing	2.6 (1.9 to 3.6)	2.8 (1.9 to 3.9)	3.7 (2.9 to 4.6)

No statistical analysis provided for Time to Deterioration for European Organisation for Research and Treatment of Cancer 35-item head and neck quality of life questionnaire (EORTC QLQ-H&N35)

14. Secondary Outcome Measure: Number of participants reporting one or more adverse events (AE) [ Time Frame: First dose to last dose + 90 days or data cut off (up to 36 months) ]

Measure Type	Secondary
Measure Name	Number of participants reporting one or more adverse events (AE)
Measure Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Inclusive of AEs and serious AEs.
Time Frame	First dose to last dose + 90 days or data cut off (up to 36 months)
Safety Issue?

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.
Safety analysis set - inclusive of all participants that received at least 1 dose of study treatment.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Measured Values

	Durvalumab + Tremelimumab	Durvalumab	Standard of Care (SoC)
Number of Participants Analyzed [units:participants]	246	237	240
Number of participants reporting one or more adverse events (AE) [units: ]	232	214	229

No statistical analysis provided for Number of participants reporting one or more adverse events (AE)

Serious Adverse Events

Time Frame	First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Additional Description	No text entered.

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Serious Adverse Events

Durvalumab + Tremelimumab

Durvalumab

Standard of Care (SoC)

Total, serious adverse events

# participants affected / at risk

79/246 (32.11%)

69/237 (29.11%)

61/240 (25.42%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

5/246 (2.03%)

0/237 (0.00%)

1/240 (0.42%)

# events

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

1/240 (0.42%)

# events

Cardiac disorders

Left ventricular failure¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Endocrine disorders

Inappropriate antidiuretic hormone secretion¹,^†

# participants affected / at risk

1/246 (0.41%)

2/237 (0.84%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Colitis ischaemic¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Gastric ulcer perforation¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Oesophageal infection¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Infections and infestations

Osteomyelitis¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Postoperative wound infection¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Staphylococcal infection¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Stoma site infection¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Infections and infestations

Subcutaneous abscess¹,^†

# participants affected / at risk

0/246 (0.00%)

2/237 (0.84%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Abdominal wall wound¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Injury, poisoning and procedural complications

Osteoradionecrosis¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Thermal burn¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthritis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Nervous system disorders

Loss of consciousness¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Nervous system disorders

Seizure¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

1/240 (0.42%)

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

1/240 (0.42%)

# events

Respiratory, thoracic and mediastinal disorders

Acquired tracheo-oesophageal fistula¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial haemorrhage¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

4/246 (1.63%)

1/237 (0.42%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory distress¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

1/240 (0.42%)

# events

Blood and lymphatic system disorders

Haemorrhagic diathesis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

2/240 (0.83%)

# events

Blood and lymphatic system disorders

Pancytopenia¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Cardiac disorders

Acute coronary syndrome¹,^†

# participants affected / at risk

2/246 (0.81%)

0/237 (0.00%)

1/240 (0.42%)

# events

Cardiac disorders

Atrial flutter¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Cardiac disorders

Pericardial effusion¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Ear and labyrinth disorders

Otorrhoea¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Endocrine disorders

Adrenal insufficiency¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Endocrine disorders

Hypopituitarism¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Eye disorders

Eye pain¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

2/246 (0.81%)

0/237 (0.00%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Coeliac disease¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/246 (0.81%)

1/237 (0.42%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

4/246 (1.63%)

1/237 (0.42%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Gastric fistula¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Gastrointestinal haemorrhage¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Inguinal hernia¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Intestinal obstruction¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Large intestine perforation¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Gastrointestinal disorders

Lower gastrointestinal haemorrhage¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Mouth haemorrhage¹,^†

# participants affected / at risk

2/246 (0.81%)

0/237 (0.00%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Tongue haemorrhage¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Upper gastrointestinal haemorrhage¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

1/240 (0.42%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

1/240 (0.42%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

2/246 (0.81%)

0/237 (0.00%)

0/240 (0.00%)

# events

General disorders and administration site conditions

Death¹,^†

# participants affected / at risk

2/246 (0.81%)

2/237 (0.84%)

2/240 (0.83%)

# events

General disorders and administration site conditions

Facial pain¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

General disorders and administration site conditions

General physical health deterioration¹,^†

# participants affected / at risk

0/246 (0.00%)

4/237 (1.69%)

1/240 (0.42%)

# events

General disorders and administration site conditions

Hyperthermia¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

General disorders and administration site conditions

Inflammation¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

4/246 (1.63%)

2/237 (0.84%)

2/240 (0.83%)

# events

General disorders and administration site conditions

Sudden cardiac death¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Immune system disorders

Anaphylactic reaction¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Immune system disorders

Drug hypersensitivity¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Abscess neck¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Abscess oral¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Bacteraemia¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

0/240 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

0/240 (0.00%)

# events

Infections and infestations

Device related infection¹,^†

# participants affected / at risk

3/246 (1.22%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Endocarditis¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Escherichia sepsis¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

1/240 (0.42%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Infection¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Infections and infestations

Localised infection¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

2/240 (0.83%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Lung infection¹,^†

# participants affected / at risk

1/246 (0.41%)

2/237 (0.84%)

2/240 (0.83%)

# events

Infections and infestations

Peritonitis¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

9/246 (3.66%)

8/237 (3.38%)

9/240 (3.75%)

# events

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Pulmonary sepsis¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Respiratory tract infection¹,^†

# participants affected / at risk

4/246 (1.63%)

1/237 (0.42%)

1/240 (0.42%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

3/246 (1.22%)

0/237 (0.00%)

4/240 (1.67%)

# events

Infections and infestations

Septic shock¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Infections and infestations

Streptococcal sepsis¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Femoral neck fracture¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Fibula fracture¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Gastrostomy tube site complication¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Nasal injury¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Periprosthetic fracture¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Petroleum distillate poisoning¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Radius fracture¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Stoma site haemorrhage¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Injury, poisoning and procedural complications

Tracheostomy malfunction¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

2/240 (0.83%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹,^†

# participants affected / at risk

2/246 (0.81%)

4/237 (1.69%)

2/240 (0.83%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

0/246 (0.00%)

2/237 (0.84%)

1/240 (0.42%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

0/246 (0.00%)

2/237 (0.84%)

0/240 (0.00%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Osteonecrosis of jaw¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Trismus¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

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

Infected neoplasm¹,^†

# participants affected / at risk

0/246 (0.00%)

2/237 (0.84%)

0/240 (0.00%)

# events

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

Tumour associated fever¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

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

Tumour haemorrhage¹,^†

# participants affected / at risk

7/246 (2.85%)

4/237 (1.69%)

2/240 (0.83%)

# events

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

Tumour necrosis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Nervous system disorders

Carotid artery disease¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

3/246 (1.22%)

0/237 (0.00%)

0/240 (0.00%)

# events

Nervous system disorders

Depressed level of consciousness¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

0/240 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Nervous system disorders

Epilepsy¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Nervous system disorders

Haemorrhagic stroke¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Nervous system disorders

Horner's syndrome¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Nervous system disorders

Presyncope¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/246 (0.41%)

2/237 (0.84%)

1/240 (0.42%)

# events

Nervous system disorders

Vocal cord paralysis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Product issues

Device dislocation¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Product issues

Device occlusion¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

2/240 (0.83%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Psychiatric disorders

Disorientation¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Psychiatric disorders

Hallucinations, mixed¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Renal and urinary disorders

Tubulointerstitial nephritis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

1/240 (0.42%)

# events

Respiratory, thoracic and mediastinal disorders

Apnoea¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Asphyxia¹,^†

# participants affected / at risk

2/246 (0.81%)

3/237 (1.27%)

3/240 (1.25%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

1/240 (0.42%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/246 (0.41%)

3/237 (1.27%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

2/246 (0.81%)

0/237 (0.00%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Laryngeal oedema¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Lung disorder¹,^†

# participants affected / at risk

0/246 (0.00%)

3/237 (1.27%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngeal haemorrhage¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration¹,^†

# participants affected / at risk

3/246 (1.22%)

5/237 (2.11%)

2/240 (0.83%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

3/246 (1.22%)

3/237 (1.27%)

1/240 (0.42%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

0/246 (0.00%)

2/237 (0.84%)

3/240 (1.25%)

# events

Respiratory, thoracic and mediastinal disorders

Sleep apnoea syndrome¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Respiratory, thoracic and mediastinal disorders

Stridor¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

0/240 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

1/240 (0.42%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

Skin and subcutaneous tissue disorders

Vasculitic ulcer¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Arterial haemorrhage¹,^†

# participants affected / at risk

2/246 (0.81%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Embolism¹,^†

# participants affected / at risk

1/246 (0.41%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Haemorrhage¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

1/240 (0.42%)

# events

Vascular disorders

Peripheral ischaemia¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Shock haemorrhagic¹,^†

# participants affected / at risk

0/246 (0.00%)

1/237 (0.42%)

0/240 (0.00%)

# events

Vascular disorders

Superior vena cava syndrome¹,^†

# participants affected / at risk

1/246 (0.41%)

0/237 (0.00%)

0/240 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 21.0

Other Adverse Events

Time Frame	First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Durvalumab + Tremelimumab	Participants received 20 mg/kg durvalumab and 1 mg/kg tremelimumab combination therapy via intravenous (IV) infusion every 4 weeks (q4w) for up to 16 weeks. 4 weeks after completion of combination therapy, participants received dosing with durvalumab 10 mg/kg monotherapy every 2 weeks (q2w) until disease progression (PD).
Durvalumab	Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).
Standard of Care (SoC)	Participants received monotherapy with 1 of the following therapies at the investigator’s discretion until disease progression (PD): cetuximab, a taxane, methotrexate, or a fluoropyrimidine.

Other Adverse Events

Durvalumab + Tremelimumab

Durvalumab

Standard of Care (SoC)

Total, other (not including serious) adverse events

# participants affected / at risk

203/246 (82.52%)

180/237 (75.95%)

207/240 (86.25%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

55/246 (22.36%)

47/237 (19.83%)

56/240 (23.33%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

3/246 (1.22%)

8/237 (3.38%)

20/240 (8.33%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

10/246 (4.07%)

2/237 (0.84%)

13/240 (5.42%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

11/246 (4.47%)

4/237 (1.69%)

32/240 (13.33%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

11/246 (4.47%)

5/237 (2.11%)

18/240 (7.50%)

# events

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

32/246 (13.01%)

33/237 (13.92%)

5/240 (2.08%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

33/246 (13.41%)

33/237 (13.92%)

29/240 (12.08%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

38/246 (15.45%)

24/237 (10.13%)

32/240 (13.33%)

# events

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

20/246 (8.13%)

28/237 (11.81%)

18/240 (7.50%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

30/246 (12.20%)

27/237 (11.39%)

41/240 (17.08%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

5/246 (2.03%)

11/237 (4.64%)

27/240 (11.25%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

15/246 (6.10%)

18/237 (7.59%)

20/240 (8.33%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

51/246 (20.73%)

42/237 (17.72%)

56/240 (23.33%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

40/246 (16.26%)

31/237 (13.08%)

35/240 (14.58%)

# events

General disorders and administration site conditions

Mucosal inflammation¹,^†

# participants affected / at risk

2/246 (0.81%)

3/237 (1.27%)

17/240 (7.08%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

31/246 (12.60%)

19/237 (8.02%)

29/240 (12.08%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

15/246 (6.10%)

11/237 (4.64%)

17/240 (7.08%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

15/246 (6.10%)

7/237 (2.95%)

14/240 (5.83%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

14/246 (5.69%)

7/237 (2.95%)

8/240 (3.33%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

17/246 (6.91%)

9/237 (3.80%)

12/240 (5.00%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

27/246 (10.98%)

31/237 (13.08%)

20/240 (8.33%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

44/246 (17.89%)

30/237 (12.66%)

48/240 (20.00%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹,^†

# participants affected / at risk

17/246 (6.91%)

10/237 (4.22%)

7/240 (2.92%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

14/246 (5.69%)

11/237 (4.64%)

8/240 (3.33%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

20/246 (8.13%)

15/237 (6.33%)

23/240 (9.58%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

11/246 (4.47%)

13/237 (5.49%)

16/240 (6.67%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

4/246 (1.63%)

5/237 (2.11%)

24/240 (10.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

13/246 (5.28%)

7/237 (2.95%)

8/240 (3.33%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

26/246 (10.57%)

25/237 (10.55%)

19/240 (7.92%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

27/246 (10.98%)

27/237 (11.39%)

19/240 (7.92%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

0/246 (0.00%)

0/237 (0.00%)

29/240 (12.08%)

# events

Skin and subcutaneous tissue disorders

Dermatitis acneiform¹,^†

# participants affected / at risk

2/246 (0.81%)

4/237 (1.69%)

17/240 (7.08%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

23/246 (9.35%)

10/237 (4.22%)

9/240 (3.75%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

18/246 (7.32%)

19/237 (8.02%)

36/240 (15.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

17/246 (6.91%)

11/237 (4.64%)

7/240 (2.92%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 21.0

Certain Agreements

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

There is NOT 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.

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
Multiple testing was performed for OS analysis in the intent-to-treat (ITT) population and OS analysis in the PD-L1 negative population for durvalumab + tremelimumab versus SoC only.

Results Point of Contact

Name/Title:	Nassim Morsli
Organization:	AstraZeneca
Phone	+44 7384 520046
E-mail:	[email protected]

Documents available

AstraZeneca Cancer Study Locator Service Phone: 877 400 4656 Email: astrazeneca@emergingmed.com
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Cancer Center Study Locator

1-877-400-4656

astrazeneca@emergingmed.com

Investigators

Principal Investigator

Nassim Morsli

Medical Director AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

AstraZeneca Cancer Study Locator Service Phone: 877 400 4656 Email: astrazeneca@emergingmed.com

Trial Results Summaries