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

• 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:

‣ Not a woman of childbearing potential (WOCBP)

⁃ 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 Immunohistochemistry (IHC) CPS 1 status by central laboratory testing

• Have results from testing of Human Papilloma Virus (HPV) status for oropharyngeal cancer