Clinical Trials /

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

Description:

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.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 209227
  • NCT ID: NCT04428333

Conditions

  • Neoplasms, Head and Neck

Interventions

DrugSynonymsArms
GSK3359609GSK3359609 + Pembrolizumab + 5-FU-platinum chemotherapy
PembrolizumabGSK3359609 + Pembrolizumab + 5-FU-platinum chemotherapy
PlaceboPlacebo + Pembrolizumab + 5-FU-platinum chemotherapy
Platinum based chemotherapyGSK3359609 + Pembrolizumab + 5-FU-platinum chemotherapy
Fluorouracil (5FU)GSK3359609 + Pembrolizumab + 5-FU-platinum chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
GSK3359609 + Pembrolizumab + 5-FU-platinum chemotherapyExperimental
  • GSK3359609
  • Pembrolizumab
  • Platinum based chemotherapy
  • Fluorouracil (5FU)
Placebo + Pembrolizumab + 5-FU-platinum chemotherapyPlacebo Comparator
  • Pembrolizumab
  • Placebo
  • Platinum based chemotherapy
  • Fluorouracil (5FU)

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS) in total population
Time Frame:Up to 66 months
Safety Issue:
Description:OS in the total population, defined as the time from the date of randomization until the date of death due to any cause.

Secondary Outcome Measures

Measure:PFS per RECIST v1.1 in the PD-L1 CPS >=1 population
Time Frame:Up to 48 months
Safety Issue:
Description: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
Measure:Milestone OS rate at 12, 24 and 36 months in total population
Time Frame:Months 12, 24 and 36
Safety Issue:
Description:Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.
Measure:Milestone OS rate at 12, 24 and 36 months in PD-L1 CPS >=1 population
Time Frame:Months 12, 24 and 36
Safety Issue:
Description:Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.
Measure:Overall Response Rate (ORR) per RECIST v1.1 in total population
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:ORR per RECIST v1.1 in PD-L1 CPS >=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:ORR is defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1.
Measure:Disease Control Rate (DCR) per RECIST v1.1 in total population
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:DCR per RECIST v1.1 in PD-L1 CPS >=1 population
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:Duration of Response (DoR) per RECIST v1.1 in total population
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:DoR per RECIST v1.1 in PD-L1 CPS >=1 population
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in total population
Time Frame:Up to 66 months
Safety Issue:
Description:Number of participants with any AEs and SAEs per International Council on Harmonization (ICH) definitions.
Measure:Number of participants with adverse Events of Special Interest (AESI) in total population
Time Frame:Up to 66 months
Safety Issue:
Description:AESI are defined as events of potential immunologic etiology, including immune-related (ir) AEs
Measure:Number of participants with AEs and SAEs in PD-L1 CPS>=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:Number of participants with any AEs and SAEs per ICH definitions.
Measure:Number of participants with AESIs in PD-L1 CPS>=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:AESI are defined as events of potential immunologic etiology, including irAEs
Measure:Severity of AEs and SAEs in total population
Time Frame:Up to 66 months
Safety Issue:
Description: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
Measure:Severity of AESIs in total population
Time Frame:Up to 66 months
Safety Issue:
Description:Severity for each AESIs will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0
Measure:Severity of AEs and SAEs in PD-L1 CPS>=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:Severity for each AE and SAE will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0
Measure:Severity of AESI in PD-L1 CPS>=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:Severity for each AESI will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0
Measure:Number of participants with dose modifications in total population
Time Frame:Up to 66 months
Safety Issue:
Description:Number of participants with dose modifications (i.e. interruptions, discontinuations) in the total populations will be reported
Measure:Number of participants with dose modifications in PD-L1 CPS>=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:Number of participants with dose modifications (i.e. interruptions, discontinuations) in the PD-L1 CPS>=1 population will be reported.
Measure:Time to deterioration in pain in total populations
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:Time to deterioration in pain in PD-L1 CPS >=1 populations
Time Frame:Up to 66 months
Safety Issue:
Description: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.
Measure:Time to deterioration in physical function in total population
Time Frame:Up to 66 months
Safety Issue:
Description:The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.
Measure:Time to deterioration in physical function in PD-L1 CPS >=1 population
Time Frame:Up to 66 months
Safety Issue:
Description:The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:GlaxoSmithKline

Trial 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

Last Updated

June 21, 2020