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

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05061420

Collaborator

(none)

160

Enrollment

Locations

Arms

27.8

Anticipated Duration (Months)

4.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 2 - Cohort A2 aims to establish proof-of-concept that SAR444245 combined with both the anti-PD1 antibody pembrolizumab and cetuximab 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-naïve after failure of no more than 2 regimens for recurrent and/or metastatic (R/M) disease.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of Head and Neck	Drug: Pembrolizumab (Keytruda®) Drug: SAR444245 (Thor-707) Drug: Cetuximab (Erbitux®)	Phase 2

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 = 735 days or until PD {cohort B2}]; max 35 cycles for SAR444245 and pembrolizumab, and until PD for cetixumab (cohort A2)]
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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Oct 8, 2021

Anticipated Primary Completion Date :

Jan 27, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A1 (sub study 01) treatment- naïve Participants with HNSCC, who are treatment-naïve for R/M disease and have a PD-L1 Combined Positive Score (CPS) ≥1, will receive 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.	Drug: Pembrolizumab (Keytruda®) 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
Experimental: Cohort A2 (sub study 02) treatment-naive Participants with HNSCC, who are treatment-naïve for R/M disease and have a PD-L1 Combined Positive Score (CPS) ≥1, will receive pembrolizumab followed by cetuximab and then SAR444245. All drugs administered by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle with additional cetuximab dosing on days 8 and 15 of each cycle. Pembrolizumab and SAR444245 dosing continues for up to 35 cycles. Cetuximab dosing continues until progressive disease.	Drug: Pembrolizumab (Keytruda®) 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 (Erbitux®) Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous Infusion
Experimental: Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments Participants with HNSCC who have received treatment with a PD1/PD-L1-based regimen & platinum-based regimen and have failed no more than 2 regimens for R/M disease, will receive pembrolizumab followed by SAR444244. Both drugs administered IV infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles	Drug: Pembrolizumab (Keytruda®) 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
Experimental: Cohort B2: (sub study 05) cetuximab- naïve Participants with R/M HNSCC, who are cetuximab-naïve, have received treatment with a platinum-based regimen, and have failed no more than 2 regimens for R/M disease, will receive treatment with cetuximab followed by SAR444245. Cetuximab IV will be given on days 1, 8, and 15 of each 21 day. SAR444245 will be administered by IV infusion on Day 1 of each 21-day treatment cycle. Dosing of both drugs is to continue until disease progression, unacceptable toxicity, or withdrawal of consent.	Drug: SAR444245 (Thor-707) Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion Drug: Cetuximab (Erbitux®) Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous Infusion

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [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]
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

Secondary Outcome Measures

To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (TEAEs) [From first IMP dose up to 30 days after the last dose of IMP]
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
To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (SAEs) [From first IMP dose up to 90 days after the last dose of IMP]
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
Time to response [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]
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.
Duration of response (DoR) [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]
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.
Clinical benefit rate (CBR) [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]
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)
Progression free survival (PFS) [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]
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
To assess the 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]
Plasma concentrations of SAR444245
To assess the immunogenicity 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) and 30 days after last IMP administration, maximum is up to approximately 24 months]
Incidence of anti-drug antibodies (ADAs) against SAR444245

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, A2 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 Cohorts A1, A2:

--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 Cohorts A2, 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 Cohorts A2, 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope-Site Number:8400007	Duarte	California	United States	91010
2	University of Colorado-Site Number:8400004	Aurora	Colorado	United States	80045
3	John D. Archbold Memorial Hospital-Site Number:8400009	Thomasville	Georgia	United States	31792
4	University of Michigan-Site Number:8400008	Ann Arbor	Michigan	United States	48109
5	Thomas Jefferson University Hospital-Site Number:8400003	Philadelphia	Pennsylvania	United States	19107
6	Seattle Cancer Care Alliance-Site Number:8400006	Seattle	Washington	United States	98115
7	Investigational Site Number :1240001	Montreal	Quebec	Canada	H4A 3J1
8	Investigational Site Number :1520003	Santiago	Reg Metropolitana De Santiago	Chile	7500921
9	Investigational Site Number :1520001	Santiago	Reg Metropolitana De Santiago	Chile	8420383
10	Investigational Site Number :1520002	Temuco		Chile	4800827
11	Investigational Site Number :1520004	Vina del Mar		Chile	2540488
12	Investigational Site Number :2500003	Bordeaux		France	33075
13	Investigational Site Number :2500008	Lyon		France	69373
14	Investigational Site Number :2500005	Nantes		France	44093
15	Investigational Site Number :2500006	Paris		France	75015
16	Investigational Site Number :2500004	Rouen		France	76038
17	Investigational Site Number :2500002	Strasbourg		France	67033
18	Investigational Site Number :2500001	Villejuif		France	94800
19	Investigational Site Number :2760004	Berlin		Germany	12200
20	Investigational Site Number :2760001	Leipzig		Germany	04103
21	Investigational Site Number :3800001	Meldola (FC)	Emilia-Romagna	Italy	47014
22	Investigational Site Number :3800003	Brescia		Italy	25123
23	Investigational Site Number :3800002	Milano		Italy	20133
24	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi	Korea, Republic of	05505
25	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi	Korea, Republic of	06351
26	Investigational Site Number :4100003	Seoul		Korea, Republic of	06591
27	Investigational Site Number :5280002	Amsterdam		Netherlands	1066
28	Investigational Site Number :5280001	Nijmegen		Netherlands	6500 HB
29	Investigational Site Number :7240001	Barcelona	Barcelona [Barcelona]	Spain	08035
30	Investigational Site Number :7240004	Barcelona	Barcelona [Barcelona]	Spain	08036
31	Investigational Site Number :7240005	Madrid	Madrid, Comunidad De	Spain	28040
32	Investigational Site Number :7240002	Madrid	Madrid, Comunidad De	Spain	28041
33	Investigational Site Number :7240003	Madrid	Madrid, Comunidad De	Spain	28046
34	Investigational Site Number :1580003	Tainan		Taiwan	704
35	Investigational Site Number :1580001	Taipei		Taiwan	10002

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT05061420

Other Study ID Numbers:

ACT16903
U1111-1251-5073
2021-002105-99

First Posted:

Sep 29, 2021

Last Update Posted:

Aug 10, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Pembrolizumab

Cetuximab

Study Results

No Results Posted as of Aug 10, 2022