Resumen

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.

Descripción detallada

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

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.

Intervenciones

drug

Pembrolizumab

Pharmaceutical Form: Concentration for solution for infusion Route of Administration: Intravenous Infusion

drug

SAR444245 (Thor-707)

Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion

drug

Cetuximab

Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous Infusion

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)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

SAR444245 (Thor-707)

Cetuximab

Ubicaciones

Investigational Site Number : 0320001

Patrocinadores