Trial Outcomes & Findings for Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (NCT NCT04428333)

Last Updated: 2024-10-09

Results Overview

OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

117 participants

Primary outcome timeframe

Up to approximately 7 months

Results posted on

2024-10-09

Participant Flow

Recruitment in the study stopped following the review of unblinded interim safety and efficacy data by IDMC, after a pre-specified futility analysis of the 209229(NCT04128696) trial. A Dear investigator letter (DIL) was issued to stop screening \& randomization of more participants in both studies. Participants discontinued feladilimab/placebo, but treatment with pembrolizumab plus fluorouracil (5FU) platinum chemotherapy continued until disease progression, death or unacceptable toxicity.

One participant was incorrectly re-randomized into the study twice and was given a new participant ID. However, the participant was considered only once for the analyses. An additional participant was randomized after the data cut off for the primary posting and received only pembrolizumab. Therefore, this participant is included in safety analysis for the end of study posting.

Participant milestones

Participant milestones
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Overall Study STARTED	57	60
Overall Study Modified Intent-to-Treat (mITT) Population	52	55
Overall Study Safety Population	51	65
Overall Study COMPLETED	37	35
Overall Study NOT COMPLETED	20	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Overall Study Physician Decision	5	6
Overall Study Withdrawal by Subject	1	3
Overall Study Study Terminated By Sponsor	14	16

Baseline Characteristics

Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=57 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=60 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Total n=117 Participants Total of all reporting groups
Age, Customized 18-64 years	37 Participants n=5 Participants	40 Participants n=7 Participants	77 Participants n=5 Participants
Age, Customized >=65-84 years	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	46 Participants n=7 Participants	93 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Missing	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	43 Participants n=5 Participants	50 Participants n=7 Participants	93 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 7 months

Population: mITT population: All randomized participants whether or not randomized intervention was administered, excluding those who were first dosed or randomized after the date of DIL requesting immediate discontinuation of feladilimab /placebo. Participants were analyzed based on the study intervention to which the participant was randomized

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=55 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Overall Survival (OS) in mITT Population	NA Months Interval 5.1 to The median was not reached at the time of data cut off. The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.	NA Months Interval 4.1 to The median was not reached at the time of data cut off. The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.

PRIMARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in mITT population are presented.

OS was defined as the time from the date of randomization until the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=49 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population	NA Months Interval 5.1 to The median was not reached at the time of data cut off. The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.	NA Months Interval 4.1 to The median was not reached at the time of data cut off. The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.

PRIMARY outcome

Timeframe: Up to approximately 7 months

Population: All participants in the mITT population were analyzed

PFS per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 was defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=55 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population	5.5 Months Interval 3.7 to 5.5	4.7 Months Interval 4.7 to 5.6

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in mITT population are presented.

PFS per RECIST v1.1 was defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever occurs first. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=49 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population	5.5 Months Interval 3.7 to 5.5	4.7 Months Interval 4.7 to 6.1

SECONDARY outcome

Timeframe: Months 12, 24 and 36

Population: mITT population. All participants were on study for \<12 months. The maximum duration of follow-up was approximately 7 months.

Milestone OS rate at 12, 24, and 36 months was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Months 12, 24 and 36

Population: Data for participants with PD-L1 CPS ≥1 in mITT population were to be presented. All participants were on study for \<12 months. The maximum duration of follow-up was approximately 7 months.

Milestone OS rate at 12, 24, and 36 months was not evaluated. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: All participants in the mITT population were analyzed

ORR per RECIST v1.1 was defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=55 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population	19.2 Percentage of participants Interval 9.6 to 32.5	23.6 Percentage of participants Interval 13.2 to 37.0

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in mITT population are presented.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=49 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population	18.4 Percentage of participants Interval 8.8 to 32.0	23.1 Percentage of participants Interval 12.5 to 36.8

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: All participants in the mITT population were analyzed

DCR per RECIST v1.1 based upon investigator assessment, was defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 15 weeks. A status of SD≥15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=55 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population	32.7 Percentage of participants Interval 20.3 to 47.1	36.4 Percentage of participants Interval 23.8 to 50.4

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in mITT population are presented.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=49 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
DCR Per RECIST v1.1 in PD-L1 CPS ≥1 Population	30.6 Percentage of participants Interval 18.3 to 45.4	34.6 Percentage of participants Interval 22.0 to 49.1

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with a best overall response of CR or PR in mITT population are presented.

DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=10 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=13 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Duration of Response (DoR) Per RECIST v1.1 in mITT Population	NA Months The median was not reached at the time of primary completion date. The upper and lower limit of the 95% CI was not calculable from the available data at the time of data cut off.	2.8 Months Interval 1.2 to 2.8

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with a best overall response of CR or PR in mITT population with PD-L1 CPS ≥1 are presented.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=9 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=12 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
DoR Per RECIST v1.1 in PD-L1 CPS ≥1 Population	NA Months The median was not reached at the time of primary completion date. The upper and lower limit of the 95% CI was not calculable from the available data at the time of data cut off.	2.8 Months Interval 1.4 to 2.8

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Safety Population: All randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the actual study intervention received. An additional participant was randomized after the data cut off and received pembrolizumab. Therefore, participant was included in safety analysis.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=51 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With Adverse Events (AEs) in Safety Population	51 Participants	65 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Safety Population. An additional participant was randomized after the data cut-off and received pembrolizumab. Therefore, this participant was included in safety analysis.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=51 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With Serious Adverse Events (SAEs) in Safety Population	23 Participants	32 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Safety Population. An additional participant was randomized after the data cut-off and received pembrolizumab. Therefore, this participant was included in safety analysis.

AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs).

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=51 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population	29 Participants	43 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Data for participants with PD-L1 CPS ≥1 in the safety population are presented. An additional participant was randomized after the data cut-off and received pembrolizumab. Therefore, this participant was included in safety analysis.

Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=48 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With AEs in Programmed Death Ligand-1 (PD-L1) Combined Positive Score (CPS ≥1) Population	48 Participants	62 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and other situations according to medical or scientific judgement. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=48 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With SAEs in PD-L1 CPS ≥1 Population	21 Participants	32 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=48 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With AESIs in PD-L1 CPS ≥1 Population	27 Participants	40 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Safety Population. An additional participant was randomized after the data cut-off and received pembrolizumab. Therefore, this participant was included in safety analysis.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=51 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Severity of AEs in Safety Population Grade 1	1 Participants	3 Participants
Severity of AEs in Safety Population Grade 2	17 Participants	15 Participants
Severity of AEs in Safety Population Grade 3	23 Participants	34 Participants
Severity of AEs in Safety Population Grade 4	4 Participants	10 Participants
Severity of AEs in Safety Population Grade 5	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Safety Population. An additional participant was randomized after the data cut-off and received pembrolizumab. Therefore, this participant was included in safety analysis.

A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity for each SAE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants experiencing SAEs of Grade \>= 3 has been presented.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=51 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Severity of SAEs in Safety Population	17 Participants	26 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

Population: Safety Population. An additional participant was randomized after the data cut-off and received pembrolizumab. Therefore, this participant was included in safety analysis.

AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants experiencing AESIs of Grade \>= 3 have been presented.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=51 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Severity of AESIs in Safety Population	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity for each AE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants experiencing AEs of Grade \>= 3 have been presented. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=48 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Severity of AEs in PD-L1 CPS ≥1 Population	30 Participants	45 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity for each SAE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants that experienced SAEs of Grade \>= 3 have been presented. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=48 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Severity of SAEs in PD-L1 CPS ≥1 Population	15 Participants	26 Participants

SECONDARY outcome

Timeframe: Up to approximately 37.2 months

AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants that experienced AESIs of Grade \>= 3 have been presented.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=48 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Severity of AESI in PD-L1 CPS ≥1 Population	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: All participants in the safety population were analyzed

Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=50 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=65 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With Dose Modifications in Safety Population Dose interruption per component - feladilimab	0 Participants	NA Participants Participants in this treatment arm were not dosed with feladilimab
Number of Participants With Dose Modifications in Safety Population Treatment discontinuation per component - feladilimab/placebo	50 Participants	56 Participants
Number of Participants With Dose Modifications in Safety Population Treatment discontinuation per component - pembrolizumab	10 Participants	15 Participants
Number of Participants With Dose Modifications in Safety Population Dose interruption per component - placebo	NA Participants Participants in this treatment arm were not dosed with placebo	0 Participants
Number of Participants With Dose Modifications in Safety Population Dose interruption per component - pembrolizumab	0 Participants	0 Participants
Number of Participants With Dose Modifications in Safety Population Dose interruption per component - carboplatin/cisplatin	1 Participants	1 Participants
Number of Participants With Dose Modifications in Safety Population Dose interruption per component - fuorouracil	0 Participants	7 Participants
Number of Participants With Dose Modifications in Safety Population Dose delays per component - feladilimab	13 Participants	NA Participants Participants in this treatment arm were not dosed with feladilimab
Number of Participants With Dose Modifications in Safety Population Dose delays per component - placebo	NA Participants Participants in this treatment arm were not dosed with placebo	12 Participants
Number of Participants With Dose Modifications in Safety Population Dose delays per component - pembrolizumab	13 Participants	13 Participants
Number of Participants With Dose Modifications in Safety Population Dose delays per component - cisplatin/carboplatin	12 Participants	9 Participants
Number of Participants With Dose Modifications in Safety Population Dose delays per component - fluorouracil	9 Participants	10 Participants
Number of Participants With Dose Modifications in Safety Population Dose Reduction per component - feladilimab	NA Participants Dose reductions were not permitted for feladilimab	NA Participants Participants in this treatment arm were not dosed with feladilimab
Number of Participants With Dose Modifications in Safety Population Dose Reduction per component - placebo	NA Participants Participants in this treatment arm were not dosed with placebo	NA Participants Dose reductions were not permitted for placebo
Number of Participants With Dose Modifications in Safety Population Dose Reduction per component - pembrolizumab	NA Participants Dose reductions were not permitted for pembrolizumab	NA Participants Dose reductions were not permitted for pembrolizumab
Number of Participants With Dose Modifications in Safety Population Dose Reduction per component - carboplatin/cisplatin	12 Participants	19 Participants
Number of Participants With Dose Modifications in Safety Population Dose Reduction per component - fluorouracil	18 Participants	21 Participants
Number of Participants With Dose Modifications in Safety Population Treatment discontinuation per component - carboplatin/cisplatin	16 Participants	18 Participants
Number of Participants With Dose Modifications in Safety Population Treatment discontinuation per component - fluorouracil	13 Participants	18 Participants

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in the safety population are presented.

Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=47 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=62 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Interruptions per component- feladilimab	0 Participants	NA Participants Participants in this treatment arm were not dosed with feladilimab
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Interruptions per component- placebo	NA Participants Participants in this treatment arm were not dosed with placebo	0 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Interruptions per component- carboplatin/cisplatin	1 Participants	1 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Interruptions per component- fluorouracil	0 Participants	7 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Delays per component - pembrolizumab	2 Participants	12 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Delays per component - carboplatin/cisplatin	11 Participants	9 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Delays per component - fluorouracil	8 Participants	9 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Reductions per component - feladilimab	NA Participants Dose reductions were not permitted for feladilimab	NA Participants Participants in this treatment arm were not dosed with feladilimab
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Reductions per component - placebo	NA Participants Participants in this treatment arm were not dosed with placebo	NA Participants Dose reductions were not permitted for placebo
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Reductions per component - pembrolizumab	NA Participants Dose reductions were not permitted for pembrolizumab	NA Participants Dose reductions were not permitted for pembrolizumab
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Reductions per component - carboplatin/cisplatin	11 Participants	16 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Reductions per component - fluorouracil	16 Participants	19 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Treatment Discontinuations per component - pembrolizumab	10 Participants	14 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Treatment Discontinuations per component - carboplatin/cisplatin	13 Participants	16 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Treatment Discontinuations per component - fluorouracil	15 Participants	16 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Interruptions per component- pembrolizumab	0 Participants	0 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Delays per component - feladilimab	12 Participants	NA Participants Participants in this treatment arm were not dosed with feladilimab
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Dose Delays per component - placebo	NA Participants Participants in this treatment arm were not dosed with placebo	11 Participants
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population Treatment Discontinuations per component - feladilimab/placebo	47 Participants	53 Participants

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: All participants in the mITT population were analyzed

TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the European Organization for Research and Treatment of Cancer Item Library(EORTC IL51) Questionnaire pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC Quality of Life Questionnaire 35-Item Head and Neck Module (QLQ-H\&N35) is a head and neck specific module with multi-item scales. The mouth pain, swallowing, speech problems, opening mouth, coughing, feeding tube, and trouble with social eating domains were administered and referred to as the EORTC IL51. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0-100. A high score represents a high/healthy level of functioning. Kaplan-Meier estimate for the median TTD is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=55 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
Time to Deterioration (TTD) in Pain in mITT Population	4.4 Months Interval 2.1 to 4.4	2.8 Months Interval 1.4 to The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in the mITT population are presented.

TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the EORTC IL51 pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC QLQ-H\&N35 is a head and neck specific module with multi-item scales. The mouth pain, swallowing, speech problems, opening mouth, coughing, feeding tube, and trouble with social eating domains were administered and referred to as the EORTC IL51. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0-100. A high score represents a high/healthy level of functioning. Kaplan-Meier estimate for the median TTD is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells to the total number of viable tumor cells.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=49 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
TTD in Pain in PD-L1 CPS ≥1 Population	3.4 Months Interval 1.3 to 4.4	2.8 Months Interval 1.4 to The upper limit of the 95% CI was not calculable from the available data at the time of data cut off.

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: All participants in the mITT population were analyzed

TTD in physical function (PF) is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the Patient-Reported Outcomes Measurement Information System - Physical Function (PROMIS PF 8c).The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning.

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=55 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
TTD in Physical Function in mITT Population	2.8 Months Interval 1.4 to The available data does not allow for the calculation of the upper limit of the 95% CI.	4.3 Months Interval 2.1 to 5.6

SECONDARY outcome

Timeframe: Up to approximately 7 months

Population: Data for participants with PD-L1 CPS ≥1 in the mITT population are presented.

TTD in PF is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the PROMIS PF 8c.The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells

Outcome measures

Outcome measures
Measure	Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy n=49 Participants Participants were administered feladilimab (humanized anti- ICOS IgG4 mAb) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.	Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy n=52 Participants Participants were administered placebo and pembrolizumab as an IV infusion along with 5 FU-platinum chemotherapy (cisplatin OR carboplatin) Q3W.
TTD in Physical Function in PD-L1 CPS ≥1 Population	4.8 Months Interval 2.1 to The available data does not allow for the calculation of the upper limit of the 95% CI.	4.3 Months Interval 2.1 to 5.6

Adverse Events

Feladilimab + Pembrolizumab + 5-FU-platinum Chemotherapy

Serious events: 23 serious events

Other events: 50 other events

Deaths: 33 deaths

Placebo + Pembrolizumab + 5-FU-platinum Chemotherapy

Serious events: 32 serious events

Other events: 63 other events

Deaths: 39 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER