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

Sanofi

Status and phase: Terminated; Phase 2

Conditions: Squamous Cell Carcinoma of Head and Neck

Treatments: Drug: Pembrolizumab; Drug: Cetuximab; Drug: SAR444245 (Thor-707)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05061420

2021-002105-99 (EudraCT Number)

ACT16903

U1111-1251-5073 (Registry Identifier)

KEYNOTE-B75 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 59 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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59 participants in 3 patient groups

Cohort A1 (sub study 01) treatment- naïve

Experimental group

Description:

Participants with HNSCC, who were treatment-naïve for R/M disease and have a PD-L1 Combined Positive Score (CPS) ≥1, received pembrolizumab followed by SAR444245. Both drugs administered by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles.

Treatment:

Drug: SAR444245 (Thor-707)

Drug: Pembrolizumab

Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments

Experimental group

Description:

Participants with HNSCC who received treatment with a PD1/PD-L1-based regimen \& platinum-based regimen and have failed no more than 2 regimens for R/M disease, received pembrolizumab followed by SAR444244. Both drugs administered IV infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles

Treatment:

Drug: SAR444245 (Thor-707)

Drug: Pembrolizumab

Cohort B2: (sub study 05) cetuximab- naïve

Experimental group

Description:

Participants with R/M HNSCC, who were cetuximab-naïve, have received treatment with a platinum-based regimen, and have failed no more than 2 regimens for R/M disease, received treatment with cetuximab followed by SAR444245. Cetuximab IV was given on days 1, 8, and 15 of each 21 day. SAR444245 was administered by IV infusion on Day 1 of each 21-day treatment cycle. Dosing of both drugs continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Treatment:

Drug: SAR444245 (Thor-707)

Drug: Cetuximab