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

NCT05061420 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: ACT16903U1111-1251-5073KEYNOTE-B752021-002105-99
• Study Type: interventional
• Target: 59
• Locations: 11 countries
• Sites: 27

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (3)

• Cohort A1: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to approximately 21 months

• Cohort B1: Objective Response Rate

  ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to approximately 21 months

• Cohort B2: Objective Response Rate

  ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to approximately 21 months

Secondary Outcomes (7)

• All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  From first dose of study treatment administration (Day 1) up to 30 days post last dose of study treatment administration, up to approximately 28 months (Cohort A1), 27 months (Cohort B1) and 26 months (Cohort B2)

• All Cohorts: Time to Response (TTR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

• All Cohorts: Duration of Response (DOR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

• All Cohorts: Clinical Benefit Rate (CBR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

• All Cohorts: Progression-Free Survival (PFS)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

Study Arms (3)

Cohort A1 (sub study 01) treatment- naïve

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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

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

Cohort B2: (sub study 05) cetuximab- naïve

EXPERIMENTAL

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.

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

Interventions

Pembrolizumab DRUG

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

Also known as: KEYTRUDA®

Cohort A1 (sub study 01) treatment- naïve; Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments

SAR444245 (Thor-707) DRUG

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

Cohort A1 (sub study 01) treatment- naïve; Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments; Cohort B2: (sub study 05) cetuximab- naïve

Cetuximab DRUG

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

Also known as: ERBITUX®

Cohort B2: (sub study 05) cetuximab- naïve

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (27)

City of Hope- Site Number : 8400007

Duarte, California, 91010, United States

Location

University of Colorado- Site Number : 8400004

Aurora, Colorado, 80045, United States

Location

University of Michigan- Site Number : 8400008

Ann Arbor, Michigan, 48109, United States

Location

Thomas Jefferson University Hospital Site Number : 8400003

Philadelphia, Pennsylvania, 19107, United States

Location

Seattle Cancer Care Alliance Site Number : 8400006

Seattle, Washington, 98115, United States

Location

Investigational Site Number : 0320001

Buenos Aires, 1012, Argentina

Location

Investigational Site Number : 1240001

Montreal, Quebec, H4A 3J1, Canada

Location

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, 7500921, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8420383, Chile

Location

Investigational Site Number : 1520004

Viña del Mar, Región de Valparaíso, 2540488, Chile

Location

Investigational Site Number : 1520002

Temuco, 4800827, Chile

Location

Investigational Site Number : 2500003

Bordeaux, 33075, France

Location

Investigational Site Number : 2500008

Lyon, 69008, France

Location

Investigational Site Number : 2500006

Paris, 75015, France

Location

Investigational Site Number : 2500002

Strasbourg, 67033, France

Location

Investigational Site Number : 2500001

Villejuif, 94800, France

Location

Investigational Site Number : 2760004

Berlin, 12200, Germany

Location

Investigational Site Number : 3800003

Brescia, 25123, Italy

Location

Investigational Site Number : 5280002

Amsterdam, 1066, Netherlands

Location

Investigational Site Number : 5280001

Nijmegen, 6500 HB, Netherlands

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 05505, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240004

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number : 7240005

Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number : 7240003

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 1580003

Tainan, 704, Taiwan

Location

Related Links

• Related Info
• ACT16903 Plain Language Results Summary

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated based on strategic sponsor decision not driven by any safety concerns.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610 ext 6#

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: September 29, 2021
• Study Start: October 8, 2021
• Primary Completion: July 21, 2023
• Study Completion: November 26, 2024
• Last Updated: September 22, 2025
• Results First Posted: September 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

FR (5); TW (1); IT (1); AR (1); KR (2); NL (2); DE (1); CA (1); ES (4); CL (4); US (5)