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Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (INDUCE-4)

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ClinicalTrials.gov Identifier: NCT04428333
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : April 6, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline

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. Approximately 640 participants will be enrolled in the study.

Condition or disease Intervention/treatment Phase
Neoplasms, Head and Neck Drug: feladilimab Drug: Pembrolizumab Drug: Placebo Drug: Platinum based chemotherapy Drug: Fluorouracil (5FU) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double blind study.
Primary Purpose: Treatment
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
Actual Study Start Date : August 13, 2020
Estimated Primary Completion Date : March 11, 2024
Estimated Study Completion Date : March 11, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy Drug: feladilimab
Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 [IgG4] monoclonal antibody [mAb]

Drug: Pembrolizumab
Humanized anti-PD-1 IgG4 mAb

Drug: Platinum based chemotherapy
Cisplatin/carboplatin

Drug: Fluorouracil (5FU)
5-fluorouracil

Placebo Comparator: Placebo + Pembrolizumab + 5-FU-platinum chemotherapy Drug: Pembrolizumab
Humanized anti-PD-1 IgG4 mAb

Drug: Placebo
Sterile normal saline

Drug: Platinum based chemotherapy
Cisplatin/carboplatin

Drug: Fluorouracil (5FU)
5-fluorouracil




Primary Outcome Measures :
  1. Overall Survival (OS) in total population [ Time Frame: Up to 66 months ]
    OS in the total population, defined as the time from the date of randomization until the date of death due to any cause.

  2. OS in programmed death receptor-ligand 1 (PD-L1) combined positive score (CPS) >=1 population [ Time Frame: Up to 66 months ]
    OS in the PD-L1 CPS >=1 population, defined as the time from the date of randomization until the date of death due to any cause

  3. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in total population [ Time Frame: Up to 48 months ]
    PFS per RECIST v1.1 in the total population, defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever occurs first.


Secondary Outcome Measures :
  1. PFS per RECIST v1.1 in the PD-L1 CPS >=1 population [ Time Frame: Up to 48 months ]
    PFS per RECIST v1.1 in the PD-L1 CPS >= 1, defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever comes first

  2. Milestone OS rate at 12, 24 and 36 months in total population [ Time Frame: Months 12, 24 and 36 ]
    Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.

  3. Milestone OS rate at 12, 24 and 36 months in PD-L1 CPS >=1 population [ Time Frame: Months 12, 24 and 36 ]
    Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.

  4. Overall Response Rate (ORR) per RECIST v1.1 in total population [ Time Frame: Up to 66 months ]
    ORR is defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1.

  5. ORR per RECIST v1.1 in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    ORR is defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1.

  6. Disease Control Rate (DCR) per RECIST v1.1 in total population [ Time Frame: Up to 66 months ]
    DCR is defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 18 weeks per RECIST v1.1.

  7. DCR per RECIST v1.1 in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    DCR is defined as the percentage of participants with a best overall response of CR or PR at any time SD meeting the minimum time of 18 weeks per RECIST v1.1.

  8. Duration of Response (DoR) per RECIST v1.1 in total population [ Time Frame: Up to 66 months ]
    DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.

  9. DoR per RECIST v1.1 in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.

  10. Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in total population [ Time Frame: Up to 66 months ]
    Number of participants with any AEs and SAEs per International Council on Harmonization (ICH) definitions.

  11. Number of participants with adverse Events of Special Interest (AESI) in total population [ Time Frame: Up to 66 months ]
    AESI are defined as events of potential immunologic etiology, including immune-related (ir) AEs

  12. Number of participants with AEs and SAEs in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Number of participants with any AEs and SAEs per ICH definitions.

  13. Number of participants with AESIs in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    AESI are defined as events of potential immunologic etiology, including irAEs

  14. Severity of AEs and SAEs in total population [ Time Frame: Up to 66 months ]
    Severity for each AE and SAE will be reported during the study and will assign a grade according to the National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v5.0

  15. Severity of AESIs in total population [ Time Frame: Up to 66 months ]
    Severity for each AESIs will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0

  16. Severity of AEs and SAEs in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Severity for each AE and SAE will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0

  17. Severity of AESI in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Severity for each AESI will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0

  18. Number of participants with dose modifications in total population [ Time Frame: Up to 66 months ]
    Number of participants with dose modifications (i.e. interruptions, discontinuations) in the total populations will be reported

  19. Number of participants with dose modifications in PD-L1 CPS>=1 population [ Time Frame: Up to 66 months ]
    Number of participants with dose modifications (i.e. interruptions, discontinuations) in the PD-L1 CPS>=1 population will be reported.

  20. Time to deterioration in pain in total populations [ Time Frame: Up to 66 months ]
    Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured participants questionnaire.

  21. Time to deterioration in pain in PD-L1 CPS >=1 populations [ Time Frame: Up to 66 months ]
    Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured participants questionnaire.

  22. Time to deterioration in physical function in total population [ Time Frame: Up to 66 months ]
    The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.

  23. Time to deterioration in physical function in PD-L1 CPS >=1 population [ Time Frame: Up to 66 months ]
    The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological or cytological documentation of 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.
  • 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.
  • Has high risk of bleeding.
  • Active tumor bleeding
  • Grade 3 or Grade 4 hypercalcemia.
  • Major surgery <=28 days prior to randomization.
  • Toxicity from previous anticancer treatment that includes: a. Grade 3/Grade 4 toxicity related to prior immunotherapy and that led to treatment discontinuation and 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 any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=3 years, curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma and/or low-risk early stage prostate cancer.
  • 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.
  • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04428333


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
Show Show 102 study locations
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04428333    
Other Study ID Numbers: 209227
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: April 6, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
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
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Fluorouracil
Pembrolizumab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological