Study of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria:

• Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapywith curative intent. Participants who refuse potentially curative salvage surgeryfor recurrent disease are ineligible.

• Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, andlarynx.

• Participants must not have received prior systemic therapy for R/M SCCHN.

• PD-L1 positive tumor status defined by CPS ≥ 1% per central laboratorydetermination.

• For participants with primary oropharyngeal tumors, documentation of HPV p16 statusbased on local institutional standard is required. HPV p16 status is not requiredfor other eligible SCCHN primary tumor sites.

• Participant must have at least 1 measurable tumor lesion per RECIST v1.1.

• Availability of archival tissue for biomarker analysis from a core or excisionalbiopsy or willingness to undergo a fresh biopsy.

• ECOG performance status of 0 or 1.

• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Progressive or recurrent disease within 6 months of the last dose of systemictreatment for locally advanced SCCHN. Prior PD-(L)1, LAG-3, or TIM-3 directedtherapy, or any other checkpoint inhibitor therapy, for SCCHN or any othermalignancy.

• Treatment with anticancer therapies or participation in another interventionalclinical study within 21 days before the first administration of study treatment.

• Presence of tumors that invade major blood vessels, as shown unequivocally byimaging, and with active bleeding.

• Participants with primary tumors of the nasopharynx, sinonasal cavity, or salivaryand are excluded.

• Less than 3-month life expectancy.

• Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities ofprior therapy.

• Participant has not recovered adequately from toxicities and/or complications fromsurgical intervention before starting study treatment.

• Palliative radiation therapy administered within 1 week before the first dose ofstudy treatment or radiation therapy in the thoracic region that is > 30 Gy within 6months before the first dose of study treatment.

• Known active CNS metastases and/or carcinomatous meningitis. Participants will beexcluded if it has been < 4 weeks since radiation therapy was delivered to the CNS.