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

Squamous Cell Carcinoma of Head and Neck Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05061420
• Other study ID #: ACT16903
• Secondary ID: U1111-1251-5073K
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 8, 2021
• Est. completion date: February 17, 2025

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: February 17, 2025
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Pembrolizumab
Pharmaceutical Form: Concentration for solution for infusion Route of Administration: Intravenous Infusion
• SAR444245 (Thor-707)
Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion
• Cetuximab
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous Infusion

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Canada	Investigational Site Number : 1240001	Montreal	Quebec
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Temuco
Chile	Investigational Site Number : 1520004	Vina del Mar	Valparaíso
France	Investigational Site Number : 2500003	Bordeaux
France	Investigational Site Number : 2500008	Lyon
France	Investigational Site Number : 2500005	Nantes
France	Investigational Site Number : 2500006	Paris
France	Investigational Site Number : 2500004	Rouen
France	Investigational Site Number : 2500002	Strasbourg
France	Investigational Site Number : 2500001	Villejuif
Germany	Investigational Site Number : 2760004	Berlin
Italy	Investigational Site Number : 3800003	Brescia
Italy	Investigational Site Number : 3800002	Milano
Italy	Investigational Site Number : 3800005	Milano
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Netherlands	Investigational Site Number : 5280002	Amsterdam
Netherlands	Investigational Site Number : 5280001	Nijmegen
Spain	Investigational Site Number : 7240001	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240005	Madrid	Madrid, Comunidad De
Taiwan	Investigational Site Number : 1580003	Tainan
United States	University of Michigan Site Number : 8400008	Ann Arbor	Michigan
United States	University of Colorado Site Number : 8400004	Aurora	Colorado
United States	City of Hope Site Number : 8400007	Duarte	California
United States	Thomas Jefferson University Hospital Site Number : 8400003	Philadelphia	Pennsylvania
United States	Seattle Cancer Care Alliance Site Number : 8400006	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Objective response rate (ORR) defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) determined by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 9 months after the last participant receive first dose
Secondary	To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (TEAEs)	Incidence of treatment-emergent adverse events (TEAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading	From first IMP dose up to 30 days after the last dose of IMP
Secondary	To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (SAEs)	Incidence of serious adverse events (SAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading	From first IMP dose up to 90 days after the last dose of IMP
Secondary	Time to response	Defined as the time from the first administration of investigational medicinal product (IMP) to the first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed and determined by investigator per RECIST 1.1.	From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary	Duration of response (DoR)	Defined as the time from first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed until documented progressive disease (PD) determined by investigator per RECIST 1.1 or death from any cause, whichever occurs first.	From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary	Clinical benefit rate (CBR)	Including confirmed Complete Response (CR) or Partial Response (PR) at any time or stable disease (SD) of at least 6 months (determined by investigator per RECIST 1.1)	Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 9 months after the last participant receive first dose
Secondary	Progression free survival (PFS)	Defined as the time from the date of first IMP administration to the date of first documented disease progression determine by Investigator as per RECIST 1.1, or death due to any cause, whichever occurs first	From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary	To assess the concentrations of SAR444245	Plasma concentrations of SAR444245	At Day1 and Day 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months
Secondary	To assess the immunogenicity of SAR444245	Incidence of anti-drug antibodies (ADAs) against SAR444245	At Day1 and Day 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days) and 30 days after last IMP administration, maximum is up to approximately 24 months