Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status; Substudy-01

Key Inclusion Criteria:

• Histologically or cytologically confirmed r/m squamous cell carcinoma of the oralcavity, oropharynx, hypopharynx, and larynx that is considered incurable by localtherapies.

• No prior systemic therapy for r/m HNSCC. Individuals who had disease progression orrecurrence more than 6 months after the last dose of curative intent systemicplatinum-containing therapy for locoregionally advanced disease are eligible.

• At least 1 measurable lesion by computed tomography or magnetic resonance imagingthat qualifies as a RECIST v1.1 target lesion at baseline.

• Have adequate tumor tissue samples preferably from lesions not irradiated prior tobiopsy (acceptable from irradiated lesions if disease progression has beendemonstrated in such lesions) to submit for central testing.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

• Known results from human papillomavirus (HPV) status test (p16 expression) fororopharyngeal carcinoma defined as p16 testing.

Key Exclusion Criteria:

• Individuals with nasopharyngeal cancer (any histology), squamous cell carcinoma ofunknown primary tumors, skin (cutaneous squamous cell carcinoma), paranasal sinuses,and salivary gland.

• Have disease that is suitable for any local therapies with curative intent.

• Individuals who had disease progression or recurrence within 6 months after the lastdose of curative intent systemic platinum-containing therapy for locoregionallyadvanced disease.

• Have a history of (noninfectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/interstitial lung disease.

• Have an active autoimmune disease that required systemic treatment in the past 2years. (ie, with use of disease-modifying agents, corticosteroids, orimmunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment.

• Prior treatment with any of the following within the specific time frame prior tothe first dose of study drug:

• Major surgery for any cause or significant traumatic injury within 4 weeksprior to the first dose of study drug. Individuals must have recoveredadequately from the toxicity and/or complications from the intervention priorto starting study drug.

• Any noninvestigational anticancer therapy (chemotherapy, biologic therapy,targeted therapy, hormone therapy, or immunotherapy, etc) within 4 weeks priorto the first dose of study drug. Concurrent use for noncancer related condition (eg, hormone replacement therapy) is acceptable.

• Any investigational drugs (drugs not marketed for any indication) within 4weeks or 5 half-lives (whichever is longer) prior to the first dose of studydrug.

• Radiation therapy within 2 weeks prior to the first dose of study drug.Individuals must have recovered to Grade ≤ 1 from all radiation-relatedtoxicities, not requiring corticosteroid, and have not experienced radiationpneumonitis.

• Received prior treatment with any anti-PD-1/PD-L1, anti-TIGIT, or other immunecheckpoint inhibitors.

• Currently receiving chronic systemic steroids (> 10 mg/day prednisone or itsequivalent). Use of topical, inhalational, intranasal, intraocular steroids, and useas premedication for hypersensitivity reactions (eg, IV contrast allergy) arepermitted.

• Any unresolved toxicity (Grade ≥ 2) per National Cancer Institute Common TerminologyCriteria for Adverse Events v5.0 from prior anticancer therapy or surgicalintervention, with the exception of alopecia, vitiligo, and the laboratorytoxicities if the laboratory thresholds defined in the inclusion criteria are met.Individuals with Grade ≤ 2 neuropathy are eligible for this study.

• Have an active second malignancy or have had an active second malignancy within 3years prior to enrollment.

• Have known active central nervous system (CNS) metastases. Individuals withpreviously treated brain metastases may participate provided they have stable CNSdisease for at least 4 weeks prior to enrollment and all neurologic symptoms havereturned to baseline, have no evidence of new or enlarging brain metastasis and arenot requiring use of steroid for at least 14 days prior to the first dose of studydrugs.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.