Trial Outcomes & Findings for Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer (NCT NCT02369874)

Last Updated: 2021-02-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

736 participants

Primary outcome timeframe

September 2015 to September 2018 (36 months)

Results posted on

2021-02-10

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	247	240	249
Overall Study Received Treatment	246	237	240
Overall Study COMPLETED	203	183	188
Overall Study NOT COMPLETED	44	57	61

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Lost to Follow-up	2	2	2
Overall Study Withdrawal by Subject	7	9	27
Overall Study Miscellaneous	1	1	0
Overall Study On Treatment/Off Study	34	45	32

Baseline Characteristics

Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.	Total n=736 Participants Total of all reporting groups
Age, Continuous	59.9 Years STANDARD_DEVIATION 9.14 • n=5 Participants	59.0 Years STANDARD_DEVIATION 10.07 • n=7 Participants	59.5 Years STANDARD_DEVIATION 10.37 • n=5 Participants	59.4 Years STANDARD_DEVIATION 9.86 • n=4 Participants
Age, Customized < 65 Years	174 Participants n=5 Participants	169 Participants n=7 Participants	171 Participants n=5 Participants	514 Participants n=4 Participants
Age, Customized >= 65 - < 75 Years	63 Participants n=5 Participants	56 Participants n=7 Participants	64 Participants n=5 Participants	183 Participants n=4 Participants
Age, Customized >= 75 Years	10 Participants n=5 Participants	15 Participants n=7 Participants	14 Participants n=5 Participants	39 Participants n=4 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	38 Participants n=7 Participants	42 Participants n=5 Participants	118 Participants n=4 Participants
Sex: Female, Male Male	209 Participants n=5 Participants	202 Participants n=7 Participants	207 Participants n=5 Participants	618 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	44 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	226 Participants n=5 Participants	223 Participants n=7 Participants	229 Participants n=5 Participants	678 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Asian	33 Participants n=5 Participants	35 Participants n=7 Participants	45 Participants n=5 Participants	113 Participants n=4 Participants
Race/Ethnicity, Customized Black Or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized White	204 Participants n=5 Participants	198 Participants n=7 Participants	189 Participants n=5 Participants	591 Participants n=4 Participants
Race/Ethnicity, Customized Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	16 Participants n=4 Participants

PRIMARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: Full analysis set - inclusive of all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.
Overall Survival (OS)	6.5 Months Interval 5.5 to 8.2	7.6 Months Interval 6.1 to 9.8	8.3 Months Interval 7.3 to 9.2

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=175 Participants 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 n=172 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=177 Participants 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.
Overall Survival (OS) in PD-L1 Negative Participants	7.8 Months Interval 5.9 to 10.3	7.6 Months Interval 6.2 to 9.5	8.0 Months Interval 6.7 to 8.9

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=72 Participants 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 n=68 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=72 Participants 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.
Overall Survival (OS) in PD-L1 Positive Participants	4.8 Months Interval 3.3 to 6.4	9.8 Months Interval 4.3 to 14.1	9.0 Months Interval 6.8 to 9.2

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: Full analysis set - inclusive of all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.
Progression Free Survival (PFS)	2.0 Months Interval 1.9 to 2.3	2.1 Months Interval 1.9 to 3.0	3.7 Months Interval 3.1 to 3.7

SECONDARY outcome

Timeframe: Assessed at randomization and every 8 weeks thereafter

Population: Full analysis set - inclusive of all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.
Objective Response Rate (ORR)	18.2 Percentage of participants Interval 13.6 to 23.6	17.9 Percentage of participants Interval 13.3 to 23.4	17.3 Percentage of participants Interval 12.8 to 22.5

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

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

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=45 Participants 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 n=43 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=43 Participants 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.
Duration of Response (DoR)	7.4 Months Interval 2.8 to Upper percentile not reached.	12.9 Months Interval 5.6 to Upper percentile not reached.	3.7 Months Interval 1.9 to 5.5

SECONDARY outcome

Timeframe: Baseline up to 6 months; baseline up to 12 months

Population: Full analysis set - inclusive of all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.
Disease Control Rate (DCR) 6 Months	25.1 Percentage of participants	24.2 Percentage of participants	24.9 Percentage of participants
Disease Control Rate (DCR) 12 Months	20.6 Percentage of participants	18.8 Percentage of participants	18.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 6 months; baseline up to 12 months

Population: Full analysis set - inclusive of all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.
Percentage of Participants Alive and Progression Free (APF) 6 Months	22.5 Percentage of participants Interval 17.4 to 28.0	25.1 Percentage of participants Interval 19.7 to 30.9	23.3 Percentage of participants Interval 17.8 to 29.3
Percentage of Participants Alive and Progression Free (APF) 12 Months	11.0 Percentage of participants Interval 7.4 to 15.5	14.4 Percentage of participants Interval 10.1 to 19.5	5.7 Percentage of participants Interval 2.8 to 10.2

SECONDARY outcome

Timeframe: 12, 18 and 24 months

Population: Full analysis set - inclusive of all randomized participants.

Percentage of participants alive at 12, 18 and 24 months using a Kaplan Meier estimate.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=247 Participants 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 n=240 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=249 Participants 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.
Percentage of Participants Alive 12 Months	30.4 Percentage of participants Interval 24.7 to 36.3	37.0 Percentage of participants Interval 30.9 to 43.1	30.5 Percentage of participants Interval 24.7 to 36.4
Percentage of Participants Alive 18 Months	21.0 Percentage of participants Interval 15.9 to 26.5	25.4 Percentage of participants Interval 19.9 to 31.3	17.8 Percentage of participants Interval 13.1 to 23.2
Percentage of Participants Alive 24 Months	13.3 Percentage of participants Interval 8.9 to 18.6	18.4 Percentage of participants Interval 13.3 to 24.1	10.3 Percentage of participants Interval 5.7 to 16.5

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=175 Participants 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 n=172 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=177 Participants 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.
Progression Free Survival (PFS) in PD-L1 Negative Participants	154 Participants	151 Participants	144 Participants

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=175 Participants 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 n=172 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=177 Participants 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.
Objective Response Rate (ORR) in PD-L1 Negative Participants	17.7 Percentage of participants Interval 12.4 to 24.2	14.0 Percentage of participants Interval 9.1 to 20.0	15.3 Percentage of participants Interval 10.3 to 21.4

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: All randomized patients who provided questionnaire data

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=227 Participants 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 n=226 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=227 Participants 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.
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) Function - Physical	2.0 Months Interval 1.9 to 3.2	2.2 Months Interval 1.9 to 3.5	3.7 Months Interval 2.3 to 4.6
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) Symptom - Fatigue	1.8 Months Interval 1.3 to 1.9	1.4 Months Interval 1.0 to 1.9	1.9 Months Interval 1.6 to 2.6
Time to Deterioration in European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire, Version 3 (EORTC QLQ-C30) Global health status/QoL	1.9 Months Interval 1.8 to 2.7	2.8 Months Interval 1.9 to 3.8	3.5 Months Interval 2.9 to 4.0

SECONDARY outcome

Timeframe: September 2015 to September 2018 (36 months)

Population: All randomized patients who provided questionnaire data

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=223 Participants 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 n=220 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=221 Participants 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.
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) Pain (Mouth/ Throat)	2.9 Months Interval 2.4 to 3.8	2.8 Months Interval 2.6 to 3.7	3.4 Months Interval 2.7 to 4.0
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) Swallowing	2.6 Months Interval 1.9 to 3.6	2.8 Months Interval 1.9 to 3.9	3.7 Months Interval 2.9 to 4.6

SECONDARY outcome

Timeframe: First dose to last dose + 90 days or data cut off (up to 36 months)

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

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.

Outcome measures

Outcome measures
Measure	Durvalumab + Tremelimumab n=246 Participants 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 n=237 Participants Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=240 Participants 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.
Number of Participants Reporting One or More Adverse Events (AE)	232 Participants	214 Participants	229 Participants

Adverse Events

Durvalumab + Tremelimumab

Serious events: 79 serious events

Other events: 203 other events

Deaths: 206 deaths

Durvalumab

Serious events: 69 serious events

Other events: 180 other events

Deaths: 186 deaths

Standard of Care (SoC)

Serious events: 61 serious events

Other events: 207 other events

Deaths: 199 deaths

Serious adverse events

Other adverse events

Additional Information

Nassim Morsli

AstraZeneca

Phone: +44 7384 520046

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Durvalumab + Tremelimumab n=246 participants at risk 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 n=237 participants at risk Participants received 10 mg/kg durvalumab via intravenous (IV) infusion every 2 weeks (q2w) until disease progression (PD).	Standard of Care (SoC) n=240 participants at risk 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.
Blood and lymphatic system disorders Anaemia	22.4% 55/246 • Number of events 68 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	19.8% 47/237 • Number of events 57 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	23.3% 56/240 • Number of events 94 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Metabolism and nutrition disorders Hypomagnesaemia	1.2% 3/246 • Number of events 3 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.4% 8/237 • Number of events 10 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	8.3% 20/240 • Number of events 25 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Blood and lymphatic system disorders Leukopenia	4.1% 10/246 • Number of events 19 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	0.84% 2/237 • Number of events 3 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	5.4% 13/240 • Number of events 42 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Blood and lymphatic system disorders Neutropenia	4.5% 11/246 • Number of events 16 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	1.7% 4/237 • Number of events 4 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	13.3% 32/240 • Number of events 86 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Blood and lymphatic system disorders Thrombocytopenia	4.5% 11/246 • Number of events 23 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	2.1% 5/237 • Number of events 11 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.5% 18/240 • Number of events 49 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Endocrine disorders Hypothyroidism	13.0% 32/246 • Number of events 33 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	13.9% 33/237 • Number of events 44 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	2.1% 5/240 • Number of events 5 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Gastrointestinal disorders Constipation	13.4% 33/246 • Number of events 37 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	13.9% 33/237 • Number of events 40 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	12.1% 29/240 • Number of events 29 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Gastrointestinal disorders Diarrhoea	15.4% 38/246 • Number of events 50 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	10.1% 24/237 • Number of events 46 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	13.3% 32/240 • Number of events 42 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Gastrointestinal disorders Dysphagia	8.1% 20/246 • Number of events 22 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	11.8% 28/237 • Number of events 30 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.5% 18/240 • Number of events 18 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Gastrointestinal disorders Nausea	12.2% 30/246 • Number of events 36 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	11.4% 27/237 • Number of events 29 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	17.1% 41/240 • Number of events 47 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Gastrointestinal disorders Stomatitis	2.0% 5/246 • Number of events 7 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	4.6% 11/237 • Number of events 12 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	11.2% 27/240 • Number of events 34 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Gastrointestinal disorders Vomiting	6.1% 15/246 • Number of events 16 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.6% 18/237 • Number of events 23 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	8.3% 20/240 • Number of events 24 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
General disorders Asthenia	20.7% 51/246 • Number of events 57 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	17.7% 42/237 • Number of events 53 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	23.3% 56/240 • Number of events 63 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
General disorders Fatigue	16.3% 40/246 • Number of events 44 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	13.1% 31/237 • Number of events 35 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	14.6% 35/240 • Number of events 44 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
General disorders Mucosal inflammation	0.81% 2/246 • Number of events 3 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	1.3% 3/237 • Number of events 3 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.1% 17/240 • Number of events 20 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
General disorders Pyrexia	12.6% 31/246 • Number of events 35 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	8.0% 19/237 • Number of events 23 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	12.1% 29/240 • Number of events 42 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Investigations Alanine aminotransferase increased	6.1% 15/246 • Number of events 20 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	4.6% 11/237 • Number of events 11 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.1% 17/240 • Number of events 28 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Investigations Aspartate aminotransferase increased	6.1% 15/246 • Number of events 17 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.0% 7/237 • Number of events 8 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	5.8% 14/240 • Number of events 23 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Investigations Blood alkaline phosphatase increased	5.7% 14/246 • Number of events 20 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.0% 7/237 • Number of events 11 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.3% 8/240 • Number of events 9 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Investigations Gamma-glutamyltransferase increased	6.9% 17/246 • Number of events 18 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.8% 9/237 • Number of events 11 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	5.0% 12/240 • Number of events 19 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Investigations Weight decreased	11.0% 27/246 • Number of events 27 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	13.1% 31/237 • Number of events 33 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	8.3% 20/240 • Number of events 22 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Metabolism and nutrition disorders Decreased appetite	17.9% 44/246 • Number of events 51 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	12.7% 30/237 • Number of events 33 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	20.0% 48/240 • Number of events 56 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Metabolism and nutrition disorders Hypercalcaemia	6.9% 17/246 • Number of events 21 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	4.2% 10/237 • Number of events 12 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	2.9% 7/240 • Number of events 8 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Metabolism and nutrition disorders Hyponatraemia	5.7% 14/246 • Number of events 16 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	4.6% 11/237 • Number of events 15 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.3% 8/240 • Number of events 8 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Musculoskeletal and connective tissue disorders Neck pain	8.1% 20/246 • Number of events 20 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	6.3% 15/237 • Number of events 16 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	9.6% 23/240 • Number of events 24 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Nervous system disorders Headache	4.5% 11/246 • Number of events 11 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	5.5% 13/237 • Number of events 15 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	6.7% 16/240 • Number of events 19 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Nervous system disorders Neuropathy peripheral	1.6% 4/246 • Number of events 4 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	2.1% 5/237 • Number of events 5 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	10.0% 24/240 • Number of events 26 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Psychiatric disorders Insomnia	5.3% 13/246 • Number of events 13 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.0% 7/237 • Number of events 7 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.3% 8/240 • Number of events 8 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Respiratory, thoracic and mediastinal disorders Cough	10.6% 26/246 • Number of events 27 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	10.5% 25/237 • Number of events 26 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.9% 19/240 • Number of events 22 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.0% 27/246 • Number of events 27 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	11.4% 27/237 • Number of events 29 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.9% 19/240 • Number of events 21 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/246 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	0.00% 0/237 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	12.1% 29/240 • Number of events 30 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.81% 2/246 • Number of events 2 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	1.7% 4/237 • Number of events 4 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	7.1% 17/240 • Number of events 18 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Skin and subcutaneous tissue disorders Pruritus	9.3% 23/246 • Number of events 28 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	4.2% 10/237 • Number of events 13 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	3.8% 9/240 • Number of events 10 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Skin and subcutaneous tissue disorders Rash	7.3% 18/246 • Number of events 20 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	8.0% 19/237 • Number of events 22 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	15.0% 36/240 • Number of events 38 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)
Vascular disorders Hypertension	6.9% 17/246 • Number of events 17 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	4.6% 11/237 • Number of events 14 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)	2.9% 7/240 • Number of events 8 • First dose to last dose + 90 days or data cut off (maximum exposure 32 months)