Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (INDUCE-4)

A Randomized, Double-Blind, Adaptive, Phase II/III Study of GSK3359609 in Combination With Pembrolizumab and 5FU-Platinum Chemotherapy Versus Placebo in Combination With Pembrolizumab Plus 5FU-Platinum Chemotherapy for First-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

The purpose of this study is to evaluate if the addition of GSK3359609 to pembrolizumab in combination with 5FU-platinum based chemotherapy improves the efficacy of the pembrolizumab combination with 5FU-platinum based chemotherapy in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This randomized, double-blinded, Phase II/III study will compare the combination of GSK3359609 with pembrolizumab and 5FU-platinum chemotherapy to placebo in combination with pembrolizumab and 5FU-platinum chemotherapy in participants with recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx or larynx.

Study Overview

• Status: Terminated
• Conditions: Neoplasms, Head and Neck
• Intervention / Treatment: Drug: Feladilimab; Drug: Pembrolizumab; Drug: Platinum based chemotherapy; Drug: Fluorouracil (5FU); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, 1012
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
    • GSK Investigational Site
  • Entre Ríos
    • Oro Verde, Entre Ríos, Argentina, E3100XAD
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DBS
      • GSK Investigational Site
  • Tucumán
    • San Miguel de Tucumán, Tucumán, Argentina, T4000
      • GSK Investigational Site
• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • GSK Investigational Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • GSK Investigational Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • GSK Investigational Site
    • Melbourne, Victoria, Australia, 3000
      • GSK Investigational Site
• Belgium
  • Bruxelles, Belgium, 1070
    • GSK Investigational Site
  • Edegem, Belgium, 2650
    • GSK Investigational Site
• Brazil
  • São Paulo, Brazil, 01246-000
    • GSK Investigational Site
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29043-260
      • GSK Investigational Site
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • GSK Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • GSK Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • GSK Investigational Site
    • London, Ontario, Canada, N6A 4G5
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • GSK Investigational Site
• Denmark
  • Koebenhavn Oe, Denmark, 2100
    • GSK Investigational Site
• France
  • Bordeaux, France, 33000
    • GSK Investigational Site
  • Lyon cedex 08, France, 69373
    • GSK Investigational Site
  • Paris, France, 75005
    • GSK Investigational Site
  • Poitiers cedex, France, 86021
    • GSK Investigational Site
  • Strasbourg, France, 67200
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 12203
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Ulm, Baden-Wuerttemberg, Germany, 89075
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • GSK Investigational Site
• Hungary
  • Nyíregyháza, Hungary, 4400
    • GSK Investigational Site
• Ireland
  • Dublin, Ireland, 8
    • GSK Investigational Site
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00144
      • GSK Investigational Site
  • Liguria
    • Savona, Liguria, Italy, 17100
      • GSK Investigational Site
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20132
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20133
      • GSK Investigational Site
  • Toscana
    • Prato, Toscana, Italy, 59100
      • GSK Investigational Site
• Japan
  • Osaka, Japan, 589-8511
    • GSK Investigational Site
  • Osaka, Japan, 541-8567
    • GSK Investigational Site
  • Tokyo, Japan, 104-0045
    • GSK Investigational Site
  • Tokyo, Japan, 135-8550
    • GSK Investigational Site
• Korea, Republic of
  • Daegu-si, Korea, Republic of, 42601
    • GSK Investigational Site
  • Gyeonggi-do, Korea, Republic of, 10408
    • GSK Investigational Site
  • Hwasun-gun, Jeollanam-do, Korea, Republic of, 58128
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 05505
    • GSK Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • GSK Investigational Site
  • Gdynia, Poland, 81-519
    • GSK Investigational Site
  • Gliwice, Poland, 44-102
    • GSK Investigational Site
  • Lublin, Poland, 20-090
    • GSK Investigational Site
  • Tomaszow Mazowiecki, Poland, 97-200
    • GSK Investigational Site
  • Warszawa, Poland, 02-781
    • GSK Investigational Site
• Romania
  • Bucuresti, Romania, 021389
    • GSK Investigational Site
  • Cluj Napoca, Romania, 400015
    • GSK Investigational Site
  • Craiova, Romania, 200347
    • GSK Investigational Site
  • Floresti, Romania, 407280
    • GSK Investigational Site
  • Otopeni, Romania, 075100
    • GSK Investigational Site
  • Suceava, Romania, 720284
    • GSK Investigational Site
• Russian Federation
  • Pushkin, Russian Federation, 196603
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28050
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
• Sweden
  • Stockholm, Sweden, SE-171 64
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • GSK Investigational Site
  • Nottingham, United Kingdom, NG5 1PB
    • GSK Investigational Site
  • Sutton, United Kingdom, SM2 5PT
    • GSK Investigational Site
• United States
  • California
    • Duarte, California, United States, 91010
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Capable of giving signed informed consent
• Male or female, age >=18 years
• HNSCC that was diagnosed as recurrent or metastatic and considered incurable by local therapies.
• Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.
• No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease and no disease progression/recurrence within 6 months of the completion of curatively intended systemic treatment).
• Measurable disease per RECIST version 1.1 guidelines
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
• Adequate organ function.
• Life expectancy of at least 12 weeks.
• Female participants: must not be pregnant, not breastfeeding, and be either not a woman of childbearing potential (WOCBP); or be a WOCBP who agrees to use a highly effective method of birth control from 30 days prior to randomization and for at least 120 days after the last dose of study treatment.
• Male participants with female partners of child-bearing potential: must agree to use a highly effective contraception while receiving study treatment and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this periods.
• Provide tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) acquired within 2 years prior to randomization for PD-L1 immunohistochemistry (IHC) testing by central laboratory.
• Have PD-L1 IHC CPS status by central laboratory testing.
• Have results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.

Exclusion Criteria:

• Prior therapy with an anti-PD-1/L1/L2, anti-Inducible T Cell Co-Stimulatory Receptor (ICOS) directed agent.
• Systemic approved or investigational anticancer therapy within 30 days or 5 half lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the date of randomization. - Has high risk of bleeding (examples include but not limited to tumors encasing or infiltrating a major vessel [i.e. carotid, jugular, bronchial artery] and/or exhibits other high-risk features such as an arteriovenous fistula)
• Active tumor bleeding - Grade 3 or Grade 4 hypercalcemia.
• Major surgery less than or equal to (<=) 28 days prior to randomization.
• Participants must have also fully recovered from any surgery (major or minor) and/or its complications before randomization
• Toxicity from previous anticancer treatment that includes: a. Grade 3/Grade 4 toxicity considered related to prior immunotherapy and that led to treatment discontinuation and b. toxicity related to prior treatment that has not resolved to <=Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be <=Grade 2).
• Received transfusion of blood products or administration of colony stimulating factors within 14 days prior to randomization.
• Central nervous system (CNS) metastases, with the following exception: Participants with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to randomization.
• Invasive malignancy or history of invasive malignancy other than disease under study within the last 3 years with the exception of: a. any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=3 years. b. curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma and/or. c. low-risk early stage prostate cancer defined as: Stage T1c or T2a with a Gleason score <=6 and prostatic-specific antigen less than (<)10 nanograms per milliliter (ng/mL) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization.
• Autoimmune disease or syndrome that required systemic treatment within the past 2 years.
• Has a diagnosis of immunodeficiency or is receiving systemic steroids (>10 milligram [mg] oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to randomization.
• Receipt of any live vaccine within 30 days prior randomization.
• Prior allogeneic/autologous bone marrow or solid organ transplantation.
• Has current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents.
• Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions.
• Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.
• Recent history of allergen desensitization therapy within 4 weeks of randomization.
• History or evidence of cardiac abnormalities within the 6 months prior to randomization which include: a. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third-degree atrioventricular block. b. Cardiomyopathy, myocardial infarction, acute coronary syndromes(including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting. c. Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system. d. Symptomatic pericarditis.
• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
• Active infection requiring systemic therapy.
• Known human immunodeficiency virus (HIV) infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active infection.
• History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the formulation.
• Known history of active tuberculosis.
• Any serious (>=Grade 3) and/or unstable pre-existing medical condition (aside from malignancy).
• Any psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the date of randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy	Drug: Feladilimab; Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb); Drug: Pembrolizumab; Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb; Drug: Platinum based chemotherapy; Cisplatin/carboplatin; Drug: Fluorouracil (5FU); 5-fluorouracil
Placebo Comparator: Placebo + Pembrolizumab + 5-FU-platinum chemotherapy	Drug: Pembrolizumab; Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb; Drug: Platinum based chemotherapy; Cisplatin/carboplatin; Drug: Fluorouracil (5FU); 5-fluorouracil; Drug: Placebo; Sterile normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in mITT Population	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.	Up to approximately 7 months
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population	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.	Up to approximately 7 months
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population	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.	Up to approximately 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population	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.	Up to approximately 7 months
Milestone OS Rate at 12, 24 and 36 Months in mITT Population	Milestone OS rate at 12, 24, and 36 months was not evaluated.	Months 12, 24 and 36
Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS ≥1 Population	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.	Months 12, 24 and 36
Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population	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.	Up to approximately 7 months
ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population	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. 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.	Up to approximately 7 months
Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population	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.	Up to approximately 7 months
DCR Per RECIST v1.1 in PD-L1 CPS ≥1 Population	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. 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.	Up to approximately 7 months
Duration of Response (DoR) Per RECIST v1.1 in mITT Population	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.	Up to approximately 7 months
DoR Per RECIST v1.1 in PD-L1 CPS ≥1 Population	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. 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.	Up to approximately 7 months
Number of Participants With Adverse Events (AEs) in Safety Population	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	Up to approximately 7 months
Number of Participants With Serious Adverse Events (SAEs) in Safety Population	SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and other situations according to medical or scientific judgement.	Up to approximately 7 months
Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population	AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated.	Up to approximately 7 months
Number of Participants With AEs in PD-L1 CPS ≥1 Population	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.	Up to approximately 7 months
Number of Participants With SAEs in PD-L1 CPS ≥1 Population	SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results 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.	Up to approximately 7 months
Number of Participants With AESIs in PD-L1 CPS ≥1 Population	AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated. 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.	Up to approximately 7 months
Severity of AEs in Safety Population	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.	Up to approximately 7 months
Severity of SAEs in Safety Population	A SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results 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 have been presented.	Up to approximately 7 months
Severity of AESIs in Safety Population	AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated. 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.	Up to approximately 7 months
Severity of AEs in PD-L1 CPS ≥1 Population	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.	Up to approximately 7 months
Severity of SAEs in PD-L1 CPS ≥1 Population	A SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results 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 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.	Up to approximately 7 months
Severity of AESI in PD-L1 CPS ≥1 Population	AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Such events recently reported after treatment with other immune modulatory therapy include colitis, uveitis, hepatitis, pneumonitis, diarrhea, endocrine disorders, and specific cutaneous toxicities, as well as other events that may be immune mediated. 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.	Up to approximately 7 months
Number of Participants With Dose Modifications in Safety Population	Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component.	Up to approximately 7 months
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population	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.	Up to approximately 7 months
Time to Deterioration (TTD) in Pain in mITT Population	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.	Up to approximately 7 months
TTD in Pain in PD-L1 CPS ≥1 Population	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.	Up to approximately 7 months
TTD in Physical Function in mITT Population	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.	Up to approximately 7 months
TTD in Physical Function in PD-L1 CPS ≥1 Population	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	Up to approximately 7 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): April 27, 2021
• Study Completion (Actual): September 19, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Pembrolizumab; Platinum-based chemotherapy; Head and neck squamous cell carcinoma; GSK3359609; 5FU; Programmed cell death receptor 1; Inducible T cell co-stimulatory receptor; Keynote-A02; Phase II/III
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Fluorouracil; Pembrolizumab
• Other Study ID Numbers: 209227; 2019-003981-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No