a study of sar444245 combined with other anticancer therapies for the treatment of participants with hnscc (master protocol) (pegathor head and neck 204)

Conditions: Squamous Cell Carcinoma of Head and Neck

Summary: the is a phase 2 multi-cohort, non-randomized, open-label, multi-center study assessing the clinical benefit of sar444245 combined with other anticancer therapies for the treatment of participants aged 18 years and older with hnscc. this study is structured as a master protocol for the investigation of sar444245 with other anticancer therapies. substudy 1-cohort a1 aims to establish proof-of-concept that sar444245 combined with the anti-pd1 antibody pembrolizumab, will result in a significant increase in the observed number of objective responses in trial participants with hnscc who are treatment-naïve for recurrent and/or metastatic (r/m) disease. substudy 4-cohort b1 aims to establish proof-of-concept that sar444245 combined with the anti-pd1 antibody pembrolizumab, will result in a significant increase in the observed number of objective responses in trial participants with hnscc who have received treatment with pd1/pd-l1 and platinum-based regimen. substudy 5-cohort b2 aims to establish proof-of-concept that sar444245 combined with cetuximab will result in a significant increase in the observed number of objective responses in trial participants with hnscc previously treated with platinum-based regimen \& cetuximab-naive after failure of no more than 2 regimens for recurrent and/or metastatic (r/m) disease.

the duration of the study for an individual patient will start from the signature of the main informed consent and include: * a screening period of up to 28 days * a treatment period \[max 35 cycles {cohort a1 and b1} = 735 days or until pd {cohort b2}\]; max 35 cycles for sar444245 and pembrolizumab\] * an end-of-treatment visit at least approximately 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier) * and a follow-up visits 3 months after treatment discontinuation and every 3 months thereafter following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier

Eligibility criteria:
inclusion criteria: -participants must be ≥ 18 years of age inclusive, at the time of signing the informed consent * histologically or cytologically confirmed diagnosis of r/m hnscc that is considered not amenable to further therapy with curative intent. the eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx (nasopharynx is excluded). * measurable disease. * baseline biopsy must be submitted for all cohort a1 core phase participants. * baseline biopsy must be submitted for all cohort b1, b2 expansion phase participants. * known hpv p16 status for oropharyngeal cancer. * participant agrees to follow protocol-specified contraception guidelines. exclusion criteria: -eastern cooperative oncology group (ecog) performance status of ≥2 * has received prior il2-based anticancer treatment. -for participants in cohort a1: prior treatment with an agent (approved or investigational) that blocks the pd-1/pd-l1 pathway (participants who joined a study with an anti-pd-1/pd-l1 in the experimental arm but have written confirmation they have not received anti-pd-1/pd-l1 are allowed). * for participants in cohort b2: prior treatment with cetuximab (prior cetuximab allowed if used for the treatment of locally advanced disease, with no progressive disease for at least 4 months from completion of prior cetuximab therapy). * for participants in cohort b2: electrolytes (magnesium, calcium, potassium) outside the normal ranges. * participants under anti-hypertensive treatment who cannot temporarily (for at least 36 hours) withhold antihypertensive medications prior to each imp dosing. * participants with baseline spo2 ≤92% (without oxygen therapy). * comorbidity requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 2 weeks of imp initiation. inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder. participants who require a brief course of steroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded.