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 ID: NCT04428333

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-12
• Study Completion Date: 2023-09-19

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.

Conditions

Neoplasms, Head and Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy

Group Type: EXPERIMENTAL

Feladilimab

Intervention Type: DRUG

Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb)

Pembrolizumab

Intervention Type: DRUG

Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb

Platinum based chemotherapy

Intervention Type: DRUG

Cisplatin/carboplatin

Fluorouracil (5FU)

Intervention Type: DRUG

5-fluorouracil

Placebo + Pembrolizumab + 5-FU-platinum chemotherapy

Group Type: PLACEBO_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb

Placebo

Intervention Type: DRUG

Sterile normal saline

Platinum based chemotherapy

Intervention Type: DRUG

Cisplatin/carboplatin

Fluorouracil (5FU)

Intervention Type: DRUG

5-fluorouracil

Interventions

Feladilimab

Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb)

Intervention Type: DRUG

Pembrolizumab

Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb

Intervention Type: DRUG

Placebo

Sterile normal saline

Intervention Type: DRUG

Platinum based chemotherapy

Cisplatin/carboplatin

Intervention Type: DRUG

Fluorouracil (5FU)

5-fluorouracil

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Duarte, California, United States

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Oro Verde Entre RIos, , Argentina

GSK Investigational Site

Rosario, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

Blacktown, , Australia

GSK Investigational Site

Heidelberg, , Australia

GSK Investigational Site

Melbourne, , Australia

GSK Investigational Site

Woolangabba, , Australia

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Edegem, , Belgium

GSK Investigational Site

Curitiba, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

Vitória, , Brazil

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Hamilton, Ontario, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Poitiers, , France

GSK Investigational Site

Strasbourg, , France

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hanover, , Germany

GSK Investigational Site

Leipzig, , Germany

GSK Investigational Site

Ulm, , Germany

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Brescia, , Italy

GSK Investigational Site

Florence, , Italy

GSK Investigational Site

Milan, , Italy

GSK Investigational Site

Napoli, , Italy

GSK Investigational Site

Roma, , Italy

GSK Investigational Site

Savona, , Italy

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Gdynia, , Poland

GSK Investigational Site

Gliwice, , Poland

GSK Investigational Site

Lublin, , Poland

GSK Investigational Site

Tomaszów Mazowiecki, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Craiova, , Romania

GSK Investigational Site

Floreşti, , Romania

GSK Investigational Site

Otopeni, , Romania

GSK Investigational Site

Suceava, , Romania

GSK Investigational Site

Pushkin, , Russia

GSK Investigational Site

Daegu, , South Korea

GSK Investigational Site

Gyeonggi-do, , South Korea

GSK Investigational Site

Hwasun, , South Korea

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Nottingham, , United Kingdom

GSK Investigational Site

Sutton, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; Denmark; France; Germany; Ireland; Italy; Japan; Poland; Romania; Russia; South Korea; Spain; Sweden; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-003981-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

209227

Identifier Type: -

Identifier Source: org_study_id