A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Has newly diagnosed unresected Locally Advanced (LA) histologically confirmed HNSCCof the oral cavity, oropharynx, hypopharynx or larynx and completed cisplatin plusradiotherapy (termed "CRT" in this protocol) with curative intent and has noevidence of distant metastatic disease.

• Has provided acceptable core or excisional biopsy obtained prior to CRT:

• PD-L1 positive tumor status

• If the primary tumor site is oropharyngeal carcinoma, the participant must havep16 immunohistochemistry (IHC) testing.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Has adequate organ function.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Has received prior radiation therapy (RT), systemic therapy, targeted therapy, orsurgery for management of head and neck cancer not considered part of CRT.Participants receiving induction chemotherapy are excluded. CRT combinations withcomponents other than cisplatin and RT (e.g., experimental agents, includingradiosensitizers/radioprotectants, cetuximab) are not eligible.

• Has cancer outside of the oropharynx, larynx, hypopharynx or oral cavity, such asnasopharyngeal, sinus, other para-nasal, or other unknown primary head and neckcancer. Has more than one primary HNSCC tumor.

• Has experienced any of the following with prior immunotherapy: any immune-relatedadverse event (irAE) of Grade ≥3, immune-related severe neurologic events of anygrade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-BarréSyndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or Drug Rash withEosinophilia and Systemic Symptoms [DRESS] syndrome), or myocarditis of any grade.Non-clinically significant laboratory abnormalities are not exclusionary.

• Has undergone any major surgical procedure or experienced significant traumaticinjury that has not resolved by the time of randomization.

• Has any history of interstitial lung disease or pneumonitis (past or current).

• Has cirrhosis of any stage or current unstable liver biliary disease perinvestigator assessment defined by the presence of ascites, encephalopathy,coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.

• Has a history or current evidence of any medical condition, therapy, or laboratoryabnormality that might confound the study results, interfere with theirparticipation for the full duration of the study intervention, or indicate it is notin the best interest of the participant to participate, in the opinion of theinvestigator.

• Is receiving any other anticancer or experimental therapy. No other experimentaltherapies (including but not limited to chemotherapy, radiation, hormonal treatment,antibody therapy, immunotherapy, gene therapy, vaccine therapy, or otherexperimental drugs) of any kind are permitted while the participant is receivingstudy intervention.

• Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or an agentdirected to another stimulatory or coinhibitory T-cell receptor [e.g., CytotoxicT-lymphocyte associated protein 4 (CTLA4), OX-40, CD137]

• Is pregnant, breastfeeding, or expecting to conceive children within the projectedduration of the study, starting with the Screening Visit through 120 days after thelast dose of study intervention.

• Has a history of severe allergic and/or anaphylactic reactions to chimeric, human orhumanized antibodies, fusion proteins, or known allergies to dostarlimab or itsexcipients.