A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)

A Phase 2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR-707) Combined With Other Anticancer Therapies for the Treatment of Participants With Head and Neck Squamous Cell Carcinoma (HNSCC)

The study was 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 was structured as a master protocol for the investigation of SAR444245 with other anticancer therapies.

Substudy 1-Cohort A1 aimed 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 were treatment-naïve for recurrent and/or metastatic (R/M) disease.

Substudy 4-Cohort B1 aimed 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 aimed 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 participant started from the signature of the main informed consent and included:

• 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 participant received another anticancer therapy, whichever was 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 was earlier

Inclusion Criteria:

-Participants were ≥ 18 years of age inclusive, at the time of signing the informed consent

• Histologically or cytologically confirmed diagnosis of R/M HNSCC that was considered not amenable to further therapy with curative intent. The eligible primary tumor locations were oropharynx, oral cavity, hypopharynx, and larynx (nasopharynx is excluded).
• Measurable disease.
• Baseline biopsy was submitted for all cohort A1 Core Phase participants.
• Baseline biopsy was submitted for all cohort B1, B2 Expansion Phase participants.
• Known HPV p16 status for oropharyngeal cancer.
• Participant agreed to follow protocol-specified contraception guidelines.

Exclusion Criteria:

-Eastern Cooperative Oncology Group (ECOG) performance status of ≥2

• Had 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 were 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) were not excluded.