Clinical trial NCT05061420: A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of Head and Neck
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-09-29
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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

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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 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 outcomes:
measure: To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (TEAEs)
timeFrame: From first IMP dose up to 30 days after the last dose of IMP
measure: To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (SAEs)
timeFrame: From first IMP dose up to 90 days after the last dose of IMP
measure: Time to response
timeFrame: 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
measure: Duration of response (DoR)
timeFrame: 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
measure: Clinical benefit rate (CBR)
timeFrame: 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
measure: Progression free survival (PFS)
timeFrame: 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
measure: To assess the concentrations of SAR444245
timeFrame: 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
measure: To assess the immunogenicity of SAR444245
timeFrame: 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
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope- Site Number : 8400007
state: California
city: Aurora
country: United States
facility: University of Colorado- Site Number : 8400004
state: Colorado
city: Ann Arbor
country: United States
facility: University of Michigan- Site Number : 8400008
state: Michigan
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital Site Number : 8400003
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance Site Number : 8400006
state: Washington
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Montreal
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Vina del Mar
country: Chile
facility: Investigational Site Number : 1520004
state: Valparaíso
city: Temuco
country: Chile
facility: Investigational Site Number : 1520002
city: Bordeaux
country: France
facility: Investigational Site Number : 2500003
city: Lyon
country: France
facility: Investigational Site Number : 2500008
city: Paris
country: France
facility: Investigational Site Number : 2500006
city: Strasbourg
country: France
facility: Investigational Site Number : 2500002
city: Villejuif
country: France
facility: Investigational Site Number : 2500001
city: Berlin
country: Germany
facility: Investigational Site Number : 2760004
city: Brescia
country: Italy
facility: Investigational Site Number : 3800003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280002
city: Nijmegen
country: Netherlands
facility: Investigational Site Number : 5280001
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240004
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240005
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
state: Madrid, Comunidad De
city: Tainan
country: Taiwan
facility: Investigational Site Number : 1580003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: