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

Phase 1

Recruiting

• Conditions: eoplasms, Head and Neck; MedDRA version: 26.1Level: PTClassification code: 10060121Term: Squamous cell carcinoma of head and neck Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508613-17-00
• Lead Sponsor: Glaxosmithkline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-08
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 864

Inclusion Criteria

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., 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. Participants with oral cavity tumors must have unresectable disease. 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., Participants must have met the following minimum requirements for CRT delivered as part of local SoC: a) For Cisplatin: Minimum cumulative exposure of 200mg/m2 as part of CRT, delivered as either Q3W (e.g. 100mg/m2 cycles), or Q1W (e.g. 40mg/m2) cycles. b) Total Radiation dose of 65 Gy to 70 Gy over 6 – 7 weeks to the high-risk disease site., Has provided acceptable core or excisional biopsy (see Laboratory Manual for detail) demonstrating: a) PD-L1 positive tumor status performed at central laboratory. b) If the primary tumor site is oropharyngeal carcinoma, the participant must have HPV results defined as p16 IHC testing 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, no additional central lab testing will be required., 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 medical monitor. 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., No history of HIV-associated non-Hodgkin lymphoma =5 years prior to study entry and no history of HIV- associated invasive cervical cancer., No treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.

Exclusion Criteria

Has received prior radiation therapy, systemic therapy, targeted therapy, or radical surgery for management of head and neck cancer not considered part of CRT., Has cancer outside of the oropharynx, larynx, hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer., Any unresolved toxicity CTCAE >Grade 2 from the prior CRT., Has a known additional malignancy that progressed or required active treatment within the past 2 years., Has Grade 3-4 bleeding due to underlying malignancy or has high risk of bleeding (examples include but not limited to tumors encasing or infiltrating a major vessel (i.e., carotid artery, jugular vein) and/or other high-risk features such as an arteriovenous fistula., Is immunocompromised in the opinion of the investigator., Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment., Has any history of interstitial lung disease or pneumonitis (past or current).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified