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

NCT04428333 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2092272019-003981-42
• Study Type: interventional
• Target: 117
• Locations: 19 countries
• Sites: 71

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

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (27)

• PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population

  Up to approximately 7 months

• Milestone OS Rate at 12, 24 and 36 Months in mITT Population

  Months 12, 24 and 36

• Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS ≥1 Population

  Months 12, 24 and 36

• Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population

  Up to approximately 7 months

• ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population

  Up to approximately 7 months

Study Arms (2)

Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy

EXPERIMENTAL

Drug: Feladilimab; Drug: Pembrolizumab; Drug: Platinum based chemotherapy; Drug: Fluorouracil (5FU)

Placebo + Pembrolizumab + 5-FU-platinum chemotherapy

PLACEBO COMPARATOR

Drug: Pembrolizumab; Drug: Placebo; Drug: Platinum based chemotherapy; Drug: Fluorouracil (5FU)

Interventions

Feladilimab DRUG

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

Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy

Pembrolizumab DRUG

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

Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy; Placebo + Pembrolizumab + 5-FU-platinum chemotherapy

Placebo DRUG

Sterile normal saline

Placebo + Pembrolizumab + 5-FU-platinum chemotherapy

Platinum based chemotherapy DRUG

Cisplatin/carboplatin

Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy; Placebo + Pembrolizumab + 5-FU-platinum chemotherapy

Fluorouracil (5FU) DRUG

5-fluorouracil

Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy; Placebo + Pembrolizumab + 5-FU-platinum chemotherapy

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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (71)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Buenos Aires, 1012, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

Oro Verde Entre RIos, E3100XAD, Argentina

Location

GSK Investigational Site

Rosario, S2000DBS, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, T4000, Argentina

Location

GSK Investigational Site

Blacktown, 2148, Australia

Location

GSK Investigational Site

Heidelberg, 3084, Australia

Location

GSK Investigational Site

Melbourne, 3000, Australia

Location

GSK Investigational Site

Woolangabba, 4102, Australia

Location

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Curitiba, 81520-060, Brazil

Location

GSK Investigational Site

São Paulo, 01246-000, Brazil

Location

GSK Investigational Site

Vitória, 29043-260, Brazil

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

Location

GSK Investigational Site

London, Ontario, N6A 4G5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 3E4, Canada

Location

GSK Investigational Site

Copenhagen, 2100, Denmark

Location

GSK Investigational Site

Bordeaux, 33000, France

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GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Paris, 75005, France

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GSK Investigational Site

Poitiers, 86021, France

Location

GSK Investigational Site

Strasbourg, 67200, France

Location

GSK Investigational Site

Berlin, 12203, Germany

Location

GSK Investigational Site

Hanover, 30625, Germany

Location

GSK Investigational Site

Leipzig, 04103, Germany

Location

GSK Investigational Site

Ulm, 89075, Germany

Location

GSK Investigational Site

Dublin, 8, Ireland

Location

GSK Investigational Site

Brescia, 25123, Italy

Location

GSK Investigational Site

Florence, 59100, Italy

Location

GSK Investigational Site

Milan, 20132, Italy

Location

GSK Investigational Site

Napoli, 80131, Italy

Location

GSK Investigational Site

Roma, 00144, Italy

Location

GSK Investigational Site

Savona, 17100, Italy

Location

GSK Investigational Site

Osaka, 541-8567, Japan

Location

GSK Investigational Site

Osaka, 589-8511, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

GSK Investigational Site

Bydgoszcz, 85-796, Poland

Location

GSK Investigational Site

Gdynia, 81-519, Poland

Location

GSK Investigational Site

Gliwice, 44-102, Poland

Location

GSK Investigational Site

Lublin, 20-090, Poland

Location

GSK Investigational Site

Tomaszów Mazowiecki, 97-200, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Bucharest, 021389, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400015, Romania

Location

GSK Investigational Site

Craiova, 200347, Romania

Location

GSK Investigational Site

Floreşti, 407280, Romania

Location

GSK Investigational Site

Otopeni, 075100, Romania

Location

GSK Investigational Site

Suceava, 720284, Romania

Location

GSK Investigational Site

Pushkin, 196603, Russia

Location

GSK Investigational Site

Daegu, 42601, South Korea

Location

GSK Investigational Site

Gyeonggi-do, 10408, South Korea

Location

GSK Investigational Site

Hwasun, 58128, South Korea

Location

GSK Investigational Site

Incheon, 21565, South Korea

Location

GSK Investigational Site

Seoul, 05505, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Stockholm, SE-171 64, Sweden

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; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Platinum Compounds; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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 is 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 either GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy or placebo in combination with pembrolizumab and 5FU-platinum chemotherapy.

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: August 12, 2020
• Primary Completion: April 27, 2021
• Study Completion: September 19, 2023
• Last Updated: October 9, 2024
• Results First Posted: May 25, 2022

Record last verified: 2024-09

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

GB (3); JP (4); FR (5); DE (4); RO (6); AR (5); BE (2); PL (6); CA (6); IT (6); KR (6); ES (6); RU (1); SE (1); AU (4); US (1); BR (3); IE (1); DK (1)