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