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 therapy with curative intent. Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible.
* Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
* Participants must not have received prior systemic therapy for R/M SCCHN.
* PD-L1 positive tumor status defined by CPS ≥ 1% per central laboratory determination.
* For participants with primary oropharyngeal tumors, documentation of HPV p16 status based on local institutional standard is required. HPV p16 status is not required for 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 excisional biopsy 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 systemic treatment for locally advanced SCCHN. Prior PD-(L)1, LAG-3, or TIM-3 directed therapy, or any other checkpoint inhibitor therapy, for SCCHN or any other malignancy.
* Treatment with anticancer therapies or participation in another interventional clinical study within 21 days before the first administration of study treatment.
* Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding.
* Participants with primary tumors of the nasopharynx, sinonasal cavity, or salivary and are excluded.
* Less than 3-month life expectancy.
* Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy.
* Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment.
* Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is \> 30 Gy within 6 months before the first dose of study treatment.
* Known active CNS metastases and/or carcinomatous meningitis. Participants will be excluded if it has been \< 4 weeks since radiation therapy was delivered to the CNS.