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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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