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

NCT04128696 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2092292019-002263-99
• Study Type: interventional
• Target: 315
• Locations: 26 countries
• Sites: 163

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

Keywords

GSK3359609; Pembrolizumab; Programmed death receptor 1-ligand 1; Head and neck squamous cell carcinoma/cancer; Inducible T cell co-stimulatory receptor; Keynote-A01; Head & neck; Phase III

Outcome Measures

Primary Outcomes (3)

• Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population

  OS was defined as the time from the date of randomization to 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 16 months

• OS in the PD-L1 Expression High (CPS ≥20) Population

  OS was defined as the time from the date of randomization to 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 16 months

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population

  PFS per 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. 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 16 months

Secondary Outcomes (23)

• PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population

  Up to approximately 16 months

• PFS Per RECIST in the PD-L1 CPS ≥20 Population

  Up to approximately 16 months

• PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population

  Up to approximately 16 months

• Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population

  12 months

• Milestone OS Rate at 24 Months in the PD-L1 CPS ≥1 Population

  24 months

Study Arms (2)

Participants receiving feladilimab and pembrolizumab

EXPERIMENTAL

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.

Drug: feladilimab; Drug: Pembrolizumab

Participants receiving placebo and pembrolizumab

ACTIVE COMPARATOR

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

Drug: Pembrolizumab; Drug: Placebo

Interventions

feladilimab DRUG

feladilimab is available as an intravenous infusion.

Participants receiving feladilimab and pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is available as an intravenous infusion.

Participants receiving feladilimab and pembrolizumab; Participants receiving placebo and pembrolizumab

Placebo DRUG

Placebo is available as an intravenous infusion.

Participants receiving placebo and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Not a woman of childbearing potential (WOCBP)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (163)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20010, United States

Location

GSK Investigational Site

St. Petersburg, Florida, 33705, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28204, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15232, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29607, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37404, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Seattle, Washington, 98108, United States

Location

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1125ABD, Argentina

Location

GSK Investigational Site

La Plata, Buenos Aires, 1900, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

San Juan, J5402DIL, Argentina

Location

GSK Investigational Site

Blacktown, New South Wales, 2148, Australia

Location

GSK Investigational Site

St Leonards, New South Wales, 2065, Australia

Location

GSK Investigational Site

Herston, Queensland, 4029, Australia

Location

GSK Investigational Site

Heidelberg, Victoria, 3084, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3000, Australia

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

GSK Investigational Site

Darlinghurst, 2010, Australia

Location

GSK Investigational Site

Vitória, Espírito Santo, 29043-260, Brazil

Location

GSK Investigational Site

Florianópolis, Santa Catarina, 88034-000, Brazil

Location

GSK Investigational Site

Barretos, São Paulo, 14784-400, Brazil

Location

GSK Investigational Site

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

GSK Investigational Site

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

GSK Investigational Site

São Paulo, 01246-000, Brazil

Location

GSK Investigational Site

São Paulo, 04014-002, Brazil

Location

GSK Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 1Z5, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 3E4, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1E2, Canada

Location

GSK Investigational Site

Québec, Quebec, G1J 1Z4, Canada

Location

GSK Investigational Site

Rimouski, Quebec, G5L 5T1, Canada

Location

GSK Investigational Site

Guangzhou, Guangdong, 510060, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510503, China

Location

GSK Investigational Site

Nanning, Guangxi, 530021, China

Location

GSK Investigational Site

Guiyang, Guizhou, 550000, China

Location

GSK Investigational Site

Wuhan, Hubei, 430022, China

Location

GSK Investigational Site

Nanchang, Jiangxi, 330029, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610000, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Bengbu, 233000, China

Location

GSK Investigational Site

Harbin, 150000, China

Location

GSK Investigational Site

Hefei, 230001, China

Location

GSK Investigational Site

Shnghai, 200126, China

Location

GSK Investigational Site

Copenhagen, DK-2100, Denmark

Location

GSK Investigational Site

Bordeaux, 33000, France

Location

GSK Investigational Site

Epagny Metz-Tessy, 74370, France

Location

GSK Investigational Site

Le Mans, 72000, France

Location

GSK Investigational Site

Lille, 59000, France

Location

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Paris, 75005, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Strasbourg, 67200, France

Location

GSK Investigational Site

Toulouse, 31059, France

Location

GSK Investigational Site

Valenciennes, 59322, France

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89075, Germany

Location

GSK Investigational Site

Aachen, North Rhine-Westphalia, 52074, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04103, Germany

Location

GSK Investigational Site

Berlin, 12200, Germany

Location

GSK Investigational Site

Hamburg, 20246, Germany

Location

GSK Investigational Site

Hamburg, 22087, Germany

Location

GSK Investigational Site

Heraklion,Crete, 71110, Greece

Location

GSK Investigational Site

Thessaloniki, 54622, Greece

Location

GSK Investigational Site

Thessaloniki, 54645, Greece

Location

GSK Investigational Site

Dublin, 8, Ireland

Location

GSK Investigational Site

Dublin, D09 V2N0, Ireland

Location

GSK Investigational Site

Jerusalem, 91120, Israel

Location

GSK Investigational Site

Petah Tikva, 49100, Israel

Location

GSK Investigational Site

Ramat Gan, 52621, Israel

Location

GSK Investigational Site

Meldola (FC), Emilia-Romagna, 47014, Italy

Location

GSK Investigational Site

Brescia, Lombardy, 25123, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20133, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Candiolo, Piedmont, 10060, Italy

Location

GSK Investigational Site

Legnago (VR), Veneto, 37045, Italy

Location

GSK Investigational Site

Chiba, 260-8717, Japan

Location

GSK Investigational Site

Chiba, 277-8577, Japan

Location

GSK Investigational Site

Ehime, 791-0280, Japan

Location

GSK Investigational Site

Fukuoka, 812-8582, Japan

Location

GSK Investigational Site

Hokkaido, 060-8648, Japan

Location

GSK Investigational Site

Hyōgo, 673-8558, Japan

Location

GSK Investigational Site

Ibaraki, 305-8576, Japan

Location

GSK Investigational Site

Kagawa, 761-0793, Japan

Location

GSK Investigational Site

Kanagawa, 259-1143, Japan

Location

GSK Investigational Site

Miyagi, 981-1293, Japan

Location

GSK Investigational Site

Niigata, 951-8520, Japan

Location

GSK Investigational Site

Numakunai, 028-3695, Japan

Location

GSK Investigational Site

Osaka, 534-0021, Japan

Location

GSK Investigational Site

Saitama, 362-0806, Japan

Location

GSK Investigational Site

Shizuoka, 411-8777, Japan

Location

GSK Investigational Site

Tokyo, 113-8431, Japan

Location

GSK Investigational Site

Tokyo, 113-8519, Japan

Location

GSK Investigational Site

Saltillo, Coahuila, 25279, Mexico

Location

GSK Investigational Site

Guadalajara, Jalisco, 44680, Mexico

Location

GSK Investigational Site

Maastricht, 6229 HX, Netherlands

Location

GSK Investigational Site

Rotterdam, 3015 GD, Netherlands

Location

GSK Investigational Site

Bergen, 5021, Norway

Location

GSK Investigational Site

Oslo, 0379, Norway

Location

GSK Investigational Site

Bydgoszcz, 85-796, Poland

Location

GSK Investigational Site

Gdynia, 81-519, Poland

Location

GSK Investigational Site

Gliwice, 44-101, Poland

Location

GSK Investigational Site

Krakow, 31-826, Poland

Location

GSK Investigational Site

Olsztyn, 10-228, Poland

Location

GSK Investigational Site

Tomaszów Mazowiecki, 97-200, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Coimbra, 3000-075, Portugal

Location

GSK Investigational Site

Lisbon, 1649-035, Portugal

Location

GSK Investigational Site

Matosinhos Municipality, 4454-509, Portugal

Location

GSK Investigational Site

Porto, 4200-072, Portugal

Location

GSK Investigational Site

Porto, 4200-319, Portugal

Location

GSK Investigational Site

Brasov, 500283, Romania

Location

GSK Investigational Site

Bucharest, 021389, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400015, Romania

Location

GSK Investigational Site

Constanța, 900591, Romania

Location

GSK Investigational Site

Craiova, 200347, Romania

Location

GSK Investigational Site

Floreşti, 407280, Romania

Location

GSK Investigational Site

Iași, 700106, Romania

Location

GSK Investigational Site

Oradea, 410469, Romania

Location

GSK Investigational Site

Otopeni, 075100, Romania

Location

GSK Investigational Site

Satu Mare, 440055, Romania

Location

GSK Investigational Site

Suceava, 720284, Romania

Location

GSK Investigational Site

Moscow, 111123, Russia

Location

GSK Investigational Site

Poselok Kuzmolovsky, 188663, Russia

Location

GSK Investigational Site

Pushkin, 196603, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Saint Petersburg, 198255, Russia

Location

GSK Investigational Site

Yaroslavl, 150054, Russia

Location

GSK Investigational Site

Busan, 49241, South Korea

Location

GSK Investigational Site

Hwasun,Jeollanam-do, 58128, South Korea

Location

GSK Investigational Site

Incheon, 21565, South Korea

Location

GSK Investigational Site

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

GSK Investigational Site

Seoul, 02841, South Korea

Location

GSK Investigational Site

Seoul, 03080, South Korea

Location

GSK Investigational Site

Seoul, 05505, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08908, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Valencia, 46009, Spain

Location

GSK Investigational Site

Zaragoza, 50009, Spain

Location

GSK Investigational Site

Sankt Gallen, 9007, Switzerland

Location

GSK Investigational Site

Zurich, 8091, Switzerland

Location

GSK Investigational Site

Changhua, 50006, Taiwan

Location

GSK Investigational Site

Kaohsiung City, 833, Taiwan

Location

GSK Investigational Site

Taipei, 10002, Taiwan

Location

GSK Investigational Site

Taipei, 112, Taiwan

Location

GSK Investigational Site

Taipei, 11490, Taiwan

Location

GSK Investigational Site

Taoyuan, 333, Taiwan

Location

GSK Investigational Site

Manchester, Lancashire, M20 4BX, United Kingdom

Location

GSK Investigational Site

London, SW3 6JJ, United Kingdom

Location

GSK Investigational Site

Nottingham, NG5 1PB, United Kingdom

Location

GSK Investigational Site

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a randomized, parallel group treatment study with eligible participants receiving GSK3359609 plus pembrolizumab or placebo plus pembrolizumab.

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 16, 2019
• Study Start: November 21, 2019
• Primary Completion: April 27, 2021
• Study Completion: June 20, 2023
• Last Updated: July 10, 2024
• Results First Posted: May 24, 2022

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

CA (9); ME (2); CH (2); US (13); GR (3); BR (7); AR (4); TW (6); IE (2); IT (6); NL (2); NO (2); ES (8); KR (8); GB (4); DK (1); JP (17); FR (10); IL (3); CN (12); AU (7); PL (7); DE (6); PT (5); RO (11); RU (6)