A Phase 3 study of Dostarlimab as Sequential Therapy after Chemoradiation compared to placebo in adult participants with Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

You may be able to join if

• Is at least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent form (ICF).
• Has newly diagnosed unresected LA histologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx or larynx and completed cisplatin plus radiotherapy (termed “CRT” in this protocol) with curative intent and has no evidence of distant metastatic disease.
• 3. Disease defined as: a) Oropharyngeal p16 positive: T4 (N0-N3), M0; N3 (T1-T4), M0 b) Oropharyngeal p16 negative: Any T3-T4 (N0-N3), M0; Any N2a-N3 (T1-T4), M0 c) Larynx/hypopharynx/oral cavity (independent of p16): Any T3-T4 (N0-N3), M0; Any N2a-N3 (T1-T4), M0. NOTE: Tumors to be staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual (Amin, 2017). NOTE: Participants with distant metastases (defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes), including central nervous system (CNS) metastases and/or carcinomatosis, are not eligible, either pre-CRT, or in the screening period post-CRT. NOTE: For eligibility assessment: TNM stage for oropharyngeal HNSCC must be based on p16 status as determined by CINtec assay.
• 4. Participants must have met the following minimum requirements for CRT delivered as part of local SoC: a. For Cisplatin: Minimum cumulative exposure of 200 mg/m2 as part of CRT, delivered as either Q3W (e.g., 100 mg/m2 cycles), or Q1W (e.g., 40 mg/m2) cycles. Dose delays and dose modification are permitted per local practice providing all other requirements are met. It is recommended that concurrent cisplatin and RT be started and completed as close to each other as possible. b. Total Radiation dose of 65 Gy to 72 Gy over 6 – 7 weeks (up to +7 days if required) to the high-risk disease site.
• 5. Has provided acceptable core or excisional biopsy obtained prior to CRT (see Laboratory Manual for detail) demonstrating: a. PD-L1 positive tumor status as defined by CPS ≥ 1 using the Agilent 22C3 assay performed at central laboratory. b. If the primary tumor site is oropharyngeal carcinoma, the participant must have HPV results defined as p16 IHC testing using the CINtec p16 histology assay and a ≥70% cutoff point (p16 IHC positive is ≥70% of carcinoma TC(s) with nuclear and cytoplasmic moderate to strong staining; see Section 8.1.5 for details). If HPV status was previously tested locally using the CINtec assay (compliant to applicable local regulation), no additional central lab testing will be required.
• 6. Participants with known HIV infection are allowed with the following requirements: a) Documented evidence of plasma HIV-1 RNA levels persistently <50 c/mL confirmed ≤3 months prior to AND at screening; Plasma HIV-1 RNA consistently <50 c/ml required; if single increase >50 c/ml occurred, they cannot have been persistent nor associated with antiretroviral resistance per investigator assessment unless undetectable viral load is defined differently by local guidelines and agreed with the sponsor’s Central Study Team. In the 3 to 12 months prior to screening, plasma HIV-1 RNA levels consistently <50 c/mL are required; if single/isolated increases ≥50 c/mL occurred and are thought to be neither persistent nor associated with antiretroviral resistance per investigator assessment, the participant would be eligible if entry criteria are otherwise met. AND b) CD4 cell count ≥350 cells/mm3 over the 12 months prior to AND at screening (and no measurement <350cells/mm3 during that time period) AND c) Is on an uninterrupted combination antiretroviral therapy (ART) regimen for at least 3 months prior to screening, with a combination ART regimen consistent with locally recommended guidelines. NOTE: Participants who test as HIV positive during Screening will not be eligible for the study by default, owing to insufficient time to meet the safety requirements described in inclusion criteria 6, a, b, and c (above).