Clinical trial NCT04428333: Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neoplasms, Head and Neck
Keywords: GSK3359609
Pembrolizumab
Programmed cell death receptor 1
Inducible T cell co-stimulatory receptor
Keynote-A02
Phase II/III
Platinum-based chemotherapy
5FU
Head and neck squamous cell carcinoma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-06-11
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a randomized, parallel group treatment study with eligible participants receiving either GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy or placebo in combination with pembrolizumab and 5FU-platinum chemotherapy.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS) in mITT Population
timeFrame: Up to approximately 7 months
measure: OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
timeFrame: Up to approximately 7 months
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population
timeFrame: Up to approximately 7 months
Secondary outcomes:
measure: PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
measure: Milestone OS Rate at 12, 24 and 36 Months in mITT Population
timeFrame: Months 12, 24 and 36
measure: Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS ≥1 Population
timeFrame: Months 12, 24 and 36
measure: Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population
timeFrame: Up to approximately 7 months
measure: ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
measure: Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population
timeFrame: Up to approximately 7 months
measure: DCR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
measure: Duration of Response (DoR) Per RECIST v1.1 in mITT Population
timeFrame: Up to approximately 7 months
measure: DoR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
measure: Number of Participants With Adverse Events (AEs) in Safety Population
timeFrame: Up to approximately 37.2 months
measure: Number of Participants With Serious Adverse Events (SAEs) in Safety Population
timeFrame: Up to approximately 37.2 months
measure: Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population
timeFrame: Up to approximately 37.2 months
measure: Number of Participants With AEs in Programmed Death Ligand-1 (PD-L1) Combined Positive Score (CPS ≥1) Population
timeFrame: Up to approximately 37.2 months
measure: Number of Participants With SAEs in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 37.2 months
measure: Number of Participants With AESIs in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 37.2 months
measure: Severity of AEs in Safety Population
timeFrame: Up to approximately 37.2 months
measure: Severity of SAEs in Safety Population
timeFrame: Up to approximately 37.2 months
measure: Severity of AESIs in Safety Population
timeFrame: Up to approximately 37.2 months
measure: Severity of AEs in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 37.2 months
measure: Severity of SAEs in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 37.2 months
measure: Severity of AESI in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 37.2 months
measure: Number of Participants With Dose Modifications in Safety Population
timeFrame: Up to approximately 7 months
measure: Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
measure: Time to Deterioration (TTD) in Pain in mITT Population
timeFrame: Up to approximately 7 months
measure: TTD in Pain in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
measure: TTD in Physical Function in mITT Population
timeFrame: Up to approximately 7 months
measure: TTD in Physical Function in PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 7 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad AutOnoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Oro Verde Entre RIos
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: San Miguel de TucumAn
country: Argentina
facility: GSK Investigational Site
city: Blacktown
country: Australia
facility: GSK Investigational Site
city: Heidelberg
country: Australia
facility: GSK Investigational Site
city: Melbourne
country: Australia
facility: GSK Investigational Site
city: Woolangabba
country: Australia
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Curitiba
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: VitOria
country: Brazil
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Koebenhavn
country: Denmark
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Lyon cedex 08
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Poitiers
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
city: Leipzig
country: Germany
facility: GSK Investigational Site
city: Ulm
country: Germany
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Savona
country: Italy
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Hwasun
country: Korea, Republic of
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdynia
country: Poland
facility: GSK Investigational Site
city: Gliwice
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Tomaszow Mazowiecki
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Floresti
country: Romania
facility: GSK Investigational Site
city: Otopeni
country: Romania
facility: GSK Investigational Site
city: Suceava
country: Romania
facility: GSK Investigational Site
city: Pushkin
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: