Back to resultsA Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)
Primary Purpose
Squamous Cell Carcinoma of Head and Neck
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pembrolizumab (Keytruda®)
SAR444245 (Thor-707)
Cetuximab (Erbitux®)
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of Head and Neck
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.
Sites / Locations
- City of Hope-Site Number:8400007
- University of Colorado-Site Number:8400004
- University of Michigan-Site Number:8400008
- Thomas Jefferson University Hospital-Site Number:8400003
- Seattle Cancer Care Alliance-Site Number:8400006
- Investigational Site Number :0320001
- Investigational Site Number :1240004
- Investigational Site Number :1240001
- Investigational Site Number :1520003
- Investigational Site Number :1520001
- Investigational Site Number :1520004
- Investigational Site Number :1520002
- Investigational Site Number :2500003
- Investigational Site Number :2500008
- Investigational Site Number :2500005
- Investigational Site Number :2500006
- Investigational Site Number :2500004
- Investigational Site Number :2500002
- Investigational Site Number :2500001
- Investigational Site Number :2760004
- Investigational Site Number :2760001
- Investigational Site Number :3800001
- Investigational Site Number :3800003
- Investigational Site Number :3800002
- Investigational Site Number :3800005
- Investigational Site Number :4100002
- Investigational Site Number :4100001
- Investigational Site Number :4100003
- Investigational Site Number :5280002
- Investigational Site Number :5280001
- Investigational Site Number :6160003
- Investigational Site Number :6160001
- Investigational Site Number :7240001
- Investigational Site Number :7240004
- Investigational Site Number :7240005
- Investigational Site Number :7240002
- Investigational Site Number :7240003
- Investigational Site Number :1580004
- Investigational Site Number :1580003
- Investigational Site Number :1580001
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
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
Arm Description
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.
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
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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.
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.
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)
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
To assess the concentrations of SAR444245
Plasma concentrations of SAR444245
To assess the immunogenicity of SAR444245
Incidence of anti-drug antibodies (ADAs) against SAR444245
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05061420
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 8, 2021 (Actual)
Primary Completion Date
July 21, 2023 (Actual)
Study Completion Date
August 13, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. 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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of Head and Neck
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort A1 (sub study 01) treatment- naïve
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort B2: (sub study 05) cetuximab- naïve
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab (Keytruda®)
Intervention Description
Pharmaceutical Form: Concentration for solution for infusion Route of Administration: Intravenous Infusion
Intervention Type
Drug
Intervention Name(s)
SAR444245 (Thor-707)
Intervention Description
Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion
Intervention Type
Drug
Intervention Name(s)
Cetuximab (Erbitux®)
Intervention Description
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous Infusion
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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
Time Frame
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 Outcome Measure Information:
Title
To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (TEAEs)
Description
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
Time Frame
From first IMP dose up to 30 days after the last dose of IMP
Title
To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (SAEs)
Description
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 Frame
From first IMP dose up to 90 days after the last dose of IMP
Title
Time to response
Description
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.
Time Frame
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
Title
Duration of response (DoR)
Description
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.
Time Frame
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
Title
Clinical benefit rate (CBR)
Description
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)
Time Frame
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
Title
Progression free survival (PFS)
Description
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
Time Frame
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
Title
To assess the concentrations of SAR444245
Description
Plasma concentrations of SAR444245
Time Frame
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
Title
To assess the immunogenicity of SAR444245
Description
Incidence of anti-drug antibodies (ADAs) against SAR444245
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope-Site Number:8400007
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Colorado-Site Number:8400004
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Michigan-Site Number:8400008
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Thomas Jefferson University Hospital-Site Number:8400003
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Seattle Cancer Care Alliance-Site Number:8400006
City
Seattle
State/Province
Washington
ZIP/Postal Code
98115
Country
United States
Facility Name
Investigational Site Number :0320001
City
Buenos Aires
Country
Argentina
Facility Name
Investigational Site Number :1240004
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Investigational Site Number :1240001
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Investigational Site Number :1520003
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7500921
Country
Chile
Facility Name
Investigational Site Number :1520001
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
8420383
Country
Chile
Facility Name
Investigational Site Number :1520004
City
Vina del Mar
State/Province
Valparaíso
ZIP/Postal Code
2540488
Country
Chile
Facility Name
Investigational Site Number :1520002
City
Temuco
ZIP/Postal Code
4800827
Country
Chile
Facility Name
Investigational Site Number :2500003
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
Investigational Site Number :2500008
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Investigational Site Number :2500005
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Investigational Site Number :2500006
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Investigational Site Number :2500004
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Investigational Site Number :2500002
City
Strasbourg
ZIP/Postal Code
67033
Country
France
Facility Name
Investigational Site Number :2500001
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Investigational Site Number :2760004
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Investigational Site Number :2760001
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Investigational Site Number :3800001
City
Meldola (FC)
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
Facility Name
Investigational Site Number :3800003
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Investigational Site Number :3800002
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Investigational Site Number :3800005
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
Investigational Site Number :4100002
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100001
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100003
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Investigational Site Number :5280002
City
Amsterdam
ZIP/Postal Code
1066
Country
Netherlands
Facility Name
Investigational Site Number :5280001
City
Nijmegen
ZIP/Postal Code
6500 HB
Country
Netherlands
Facility Name
Investigational Site Number :6160003
City
Tomaszow Mazowiecki
State/Province
Lódzkie
ZIP/Postal Code
97-200
Country
Poland
Facility Name
Investigational Site Number :6160001
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Investigational Site Number :7240001
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08035
Country
Spain
Facility Name
Investigational Site Number :7240004
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number :7240005
City
Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28040
Country
Spain
Facility Name
Investigational Site Number :7240002
City
Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28041
Country
Spain
Facility Name
Investigational Site Number :7240003
City
Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28046
Country
Spain
Facility Name
Investigational Site Number :1580004
City
Kaohsiung 833
ZIP/Postal Code
833
Country
Taiwan
Facility Name
Investigational Site Number :1580003
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
Investigational Site Number :1580001
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)
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