Clinical Trials /

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

NCT04128696

Description:

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. Approximately 600 participants will be enrolled in the study and will have a follow-up until death.

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 and Pembrolizumab in Programmed Death Receptor 1-ligand 1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
  • Official Title: A Randomized, Double-blind, Adaptive, Phase II/III Study of GSK3359609 or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1 Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 209229
  • NCT ID: NCT04128696

Conditions

  • Neoplasms, Head and Neck

Interventions

DrugSynonymsArms
GSK3359609Participants receiving GSK3359609 and pembrolizumab
PembrolizumabParticipants receiving GSK3359609 and pembrolizumab
PlaceboParticipants receiving placebo and pembrolizumab

Purpose

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. Approximately 600 participants will be enrolled in the study and will have a follow-up until death.

Trial Arms

NameTypeDescriptionInterventions
Participants receiving GSK3359609 and pembrolizumabExperimentalParticipants will be administered GSK3359609 (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.
  • GSK3359609
  • Pembrolizumab
Participants receiving placebo and pembrolizumabActive ComparatorParticipants will be administered placebo and pembrolizumab (humanized anti-PD-1 IgG4 mAb) as an IV infusion once every three weeks.
  • Pembrolizumab
  • Placebo

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 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.

          -  Toxicity from previous anticancer treatment that includes 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS) in the PD-L1 expression positive (CPS >=1) population
Time Frame:Up to 4 years
Safety Issue:
Description:OS is defined as the time from the date of randomization to the date of death due to any cause.

Secondary Outcome Measures

Measure:PFS per immune-based RECIST (iRECIST) in the PD-L1 CPS >=1 population
Time Frame:Up to 3 years
Safety Issue:
Description:PFS per iRECIST is defined as the time from the date of randomization to the date of first documented disease progression confirmed consecutively per iRECIST.
Measure:PFS per RECIST v1.1 in the PD-L1 CPS >=20 population
Time Frame:Up to 3 years
Safety Issue:
Description:PFS per RECIST v1.1 is defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1.
Measure:PFS per iRECIST (iPFS) in the PD-L1 CPS >=20 population
Time Frame:Up to 3 years
Safety Issue:
Description:PFS per iRECIST is defined as the time from the date of randomization to the date of first documented disease progression confirmed consecutively per iRECIST.
Measure:Milestone OS rate at 12 months in the PD-L1 CPS >=1 population
Time Frame:Up to 12 months
Safety Issue:
Description:Milestone OS rate at 12 months will be evaluated from the survival curves.
Measure:Milestone OS rate at 24 months in the PD-L1 CPS >=1 population
Time Frame:Up to 24 months
Safety Issue:
Description:Milestone OS rate at 24 months will be evaluated from the survival curves.
Measure:Milestone OS rate at 12 months in the PD-L1 CPS >=20 population
Time Frame:Up to 12 months
Safety Issue:
Description:Milestone OS rate at 12 months will be evaluated from the survival curves.
Measure:Milestone OS rate at 24 months in the PD-L1 CPS >=20 population
Time Frame:Up to 24 months
Safety Issue:
Description:Milestone OS rate at 24 months will be evaluated from the survival curves.
Measure:Overall response rate (ORR) per RECIST v1.1 in the PD-L1 CPS >=1 population
Time Frame:Up to 3 years
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 the PD-L1 CPS >=20 population
Time Frame:Up to 3 years
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 the PD-L1 CPS >=1 population
Time Frame:Up to 3 years
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 15 weeks per RECIST v1.1.
Measure:DCR per RECIST v1.1 in the PD-L1 CPS >=20 population
Time Frame:Up to 3 years
Safety Issue:
Description:DCR is defined as the percentage of participants with a best overall response of CR or PR at any time plus SD meeting the minimum time of 15 weeks per RECIST v1.1.
Measure:Duration of response (DoR) per RECIST v1.1 in the PD-L1 CPS >=1 population
Time Frame:Up to 3 years
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 the PD-L1 CPS >=20 population
Time Frame:Up to 3 years
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 any adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with any adverse events (AEs) and serious adverse events (SAEs) per ICH definitions.
Measure:Number of participants with adverse events of special interest (AESI)
Time Frame:Up to 4 years
Safety Issue:
Description:AESI are defined as events of potential immunologic etiology, including immune-related AEs (irAEs).
Measure:Number of participants with dose modifications
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with dose modifications (i.e. interruptions, discontinuations) will be reported.
Measure:Time to deterioration in pain in the PD-L1 CPS >=1 population
Time Frame:Up to 4 years
Safety Issue:
Description:The time to deterioration in pain will be measured by structured patients questionnaire.
Measure:Time to deterioration in pain in the PD-L1 CPS >=20 population
Time Frame:Up to 4 years
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 patients questionnaire.
Measure:Time to deterioration in physical function in the PD-L1 CPS >=1 population
Time Frame:Up to 4 years
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 the PD-L1 CPS >=20 population
Time Frame:Up to 4 years
Safety Issue:
Description:Time to deterioration in physical function is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured patients questionnaire.

Details

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

Trial 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

Last Updated

October 15, 2019