Study of GSK3359609 and Pembrolizumab in Programmed Death Receptor 1-ligand 1 (PD-L1) Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

NCT ID: NCT04128696

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 315 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-21
• Study Completion Date: 2023-06-20

Brief Summary

The purpose of study is to evaluate if the addition of GSK3359609 to pembrolizumab as first-line treatment improves the efficacy of pembrolizumab in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma/cancer (HNSCC).This is a randomized, double-blind, adaptive Phase II/III study comparing a combination of GSK3359609 inducible T cell co-stimulatory receptor (ICOS) agonist and pembrolizumab to pembrolizumab plus placebo in participants with programmed death receptor 1-ligand 1 (PD-L1) combined positive score (CPS) >=1 R/M HNSCC.

Conditions

Neoplasms, Head and Neck

Study Design

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

Study Groups

Participants receiving feladilimab and pembrolizumab

Participants were administered feladilimab (humanized anti-ICOS immunoglobulin G4 \[IgG4\] monoclonal antibody \[mAb\]) and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an intravenous (IV) infusion once every three weeks.

Group Type: EXPERIMENTAL

feladilimab

Intervention Type: DRUG

feladilimab is available as an intravenous infusion.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is available as an intravenous infusion.

Participants receiving placebo and pembrolizumab

Participants were administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion once every three weeks.

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is available as an intravenous infusion.

Placebo

Intervention Type: DRUG

Placebo is available as an intravenous infusion.

Interventions

feladilimab

feladilimab is available as an intravenous infusion.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is available as an intravenous infusion.

Intervention Type: DRUG

Placebo

Placebo is available as an intravenous infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Capable of giving signed informed consent
• Male or female, age >=18 years
• Histological or cytological documentation of Head and Neck Squamous Cell Carcinoma (HNSCC) that is 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 (except for systemic therapy given as part of multimodal treatment for locally advanced disease)
• Measurable disease per RECIST version 1.1 guidelines
• ECOG Performance 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 at least one of the following conditions apply:

1. Not a woman of childbearing potential (WOCBP)

2. A WOCBP who agrees to use a 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 period
• 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 Immunohistochemistry (IHC) CPS 1 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 and/or anti-ICOS directed agent
• Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter
• Major surgery 28 days prior to randomization
• Has high risk of bleeding
• 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, except as noted below:

a. Any other invasive malignancy for which the participant was definitively treated, has been disease-free for 3 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical study

• Autoimmune disease or syndrome that required systemic treatment within the past 2 years
• Has a diagnosis of immunodeficiency or is receiving systemic steroids (≥10 mg oral prednisone per day 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
• Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice
• Active infection requiring systemic therapy
• Known 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 any ingredient used in the study treatment formulations
• Known history of active tuberculosis
• Any serious and/or unstable pre-existing medical (aside from malignancy), 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 (unless in follow-up phase and 4 weeks have elapsed from last dose of prior investigational agent), or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to date of randomization
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study

• 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

Washington D.C., District of Columbia, United States

GSK Investigational Site

St. Petersburg, Florida, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Chattanooga, Tennessee, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

La Plata, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

San Juan, , Argentina

GSK Investigational Site

Blacktown, New South Wales, Australia

GSK Investigational Site

St Leonards, New South Wales, Australia

GSK Investigational Site

Herston, Queensland, Australia

GSK Investigational Site

Heidelberg, Victoria, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Darlinghurst, , Australia

GSK Investigational Site

Vitória, Espírito Santo, Brazil

GSK Investigational Site

Florianópolis, Santa Catarina, Brazil

GSK Investigational Site

Barretos, São Paulo, Brazil

GSK Investigational Site

São José do Rio Preto, São Paulo, Brazil

GSK Investigational Site

Belo Horizonte, Minas Gerais, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Hamilton, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Rimouski, Quebec, Canada

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Nanning, Guangxi, China

GSK Investigational Site

Guiyang, Guizhou, China

GSK Investigational Site

Wuhan, Hubei, China

GSK Investigational Site

Nanchang, Jiangxi, China

GSK Investigational Site

Chengdu, Sichuan, China

GSK Investigational Site

Chengdu, Sichuan, China

GSK Investigational Site

Bengbu, , China

GSK Investigational Site

Harbin, , China

GSK Investigational Site

Hefei, , China

GSK Investigational Site

Shnghai, , China

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Epagny Metz-Tessy, , France

GSK Investigational Site

Le Mans, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Saint-Herblain, , France

GSK Investigational Site

Strasbourg, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Valenciennes, , France

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Aachen, North Rhine-Westphalia, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Heraklion,Crete, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Jerusalem, , Israel

GSK Investigational Site

Petah Tikva, , Israel

GSK Investigational Site

Ramat Gan, , Israel

GSK Investigational Site

Meldola (FC), Emilia-Romagna, Italy

GSK Investigational Site

Brescia, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Candiolo, Piedmont, Italy

GSK Investigational Site

Legnago (VR), Veneto, Italy

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Ehime, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Niigata, , Japan

GSK Investigational Site

Numakunai, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Saitama, , Japan

GSK Investigational Site

Shizuoka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Saltillo, Coahuila, Mexico

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Maastricht, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Gdynia, , Poland

GSK Investigational Site

Gliwice, , Poland

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Olsztyn, , Poland

GSK Investigational Site

Tomaszów Mazowiecki, , Poland

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Warsaw, , Poland

GSK Investigational Site

Coimbra, , Portugal

GSK Investigational Site

Lisbon, , Portugal

GSK Investigational Site

Matosinhos Municipality, , Portugal

GSK Investigational Site

Porto, , Portugal

GSK Investigational Site

Porto, , Portugal

GSK Investigational Site

Brasov, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Constanța, , Romania

GSK Investigational Site

Craiova, , Romania

GSK Investigational Site

Floreşti, , Romania

GSK Investigational Site

Iași, , Romania

GSK Investigational Site

Oradea, , Romania

GSK Investigational Site

Otopeni, , Romania

GSK Investigational Site

Satu Mare, , Romania

GSK Investigational Site

Suceava, , Romania

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Poselok Kuzmolovsky, , Russia

GSK Investigational Site

Pushkin, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Busan, , South Korea

GSK Investigational Site

Hwasun,Jeollanam-do, , South Korea

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Seongnam-si, Gyeonggi-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Pozuelo de Alarcón/Madrid, , Spain

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Santiago de Compostela, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Zaragoza, , Spain

GSK Investigational Site

Sankt Gallen, , Switzerland

GSK Investigational Site

Zurich, , Switzerland

GSK Investigational Site

Changhua, , Taiwan

GSK Investigational Site

Kaohsiung City, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taoyuan, , Taiwan

GSK Investigational Site

Manchester, Lancashire, United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Nottingham, , United Kingdom

GSK Investigational Site

Sutton, , United Kingdom

Countries

United States; Argentina; Australia; Brazil; Canada; China; Denmark; France; Germany; Greece; Ireland; Israel; Italy; Japan; Mexico; Netherlands; Norway; Poland; Portugal; Romania; Russia; South Korea; Spain; Switzerland; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002263-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

209229

Identifier Type: -

Identifier Source: org_study_id