A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)
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| ClinicalTrials.gov Identifier: NCT05104567 |
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Recruitment Status :
Active, not recruiting
First Posted : November 3, 2021
Last Update Posted : February 15, 2023
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Sponsor:
Sanofi
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Sanofi
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Brief Summary:
The study is 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 aged 18 years and older with advanced and metastatic gastrointestinal cancer. This study is structured as a master protocol for the investigation of SAR444245 with other anticancer therapies.
Sub study 01 - Cohort A aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Sub study 02 - Cohort B1, B2 and B3 would focus on non MSI-H tumors with a large unmet need to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), especially with low PD-L1 expression or after progression on prior PD1/PD-L1-based regimens.
Sub study 03 - Cohort C aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in participants with advanced unresectable or metastatic HCC who relapsed on prior PD1/PD-L1-based regimens.
Sub study 04 - Cohort D1 and D2 aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with either the anti-PD1 antibody pembrolizumab or with the anti-EGFR IgG1 antibody cetuximab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic colorectal cancer (mCRC).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Oesophageal Squamous Cell Carcinoma Gastric Cancer Hepatocellular Carcinoma Colorectal Cancer Oseophageal Adenocarcinoma | Drug: THOR-707 Drug: Pembrolizumab Drug: Cetuximab | Phase 2 |
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 A; B1,B2, B3, C and D1} = 735 days or until PD {cohort D2}], an end-of-treatment visit at least 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 280 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 Advanced and Metastatic Gastrointestinal Cancer |
| Actual Study Start Date : | December 9, 2021 |
| Estimated Primary Completion Date : | July 26, 2023 |
| Estimated Study Completion Date : | January 23, 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort A (Sub-study 01): 2-3L ESCC Post PD-1/PD-L1
SAR444245 and pembrolizumab are administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion
Other Name: Keytruda® |
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Experimental: Cohort B1 (Sub-study 02): 1-3L GC/GEJ PD1/PD-L1 naïve non-MSI-H CPS ≥1
SAR444245 and pembrolizumab are administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion
Other Name: Keytruda® |
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Experimental: Cohort B2 (Sub-study 02): 1-3L GC/GEJ PD1/PD-L1 naïve non-MSI-H CPS < 1
SAR444245 and pembrolizumab are administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion
Other Name: Keytruda® |
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Experimental: Cohort B3 (Sub-study 02): 2-4L GC/GEJ Post PD1/PD-L1 non-MSI-H
SAR444245 and pembrolizumab are administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion
Other Name: Keytruda® |
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Experimental: Cohort C (Sub-study 03): 2-3L HCC Post PD-1/PD-L1
SAR444245 and pembrolizumab are administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion
Other Name: Keytruda® |
|
Experimental: Cohort D1 (Sub-study 04): 3-6L CRC non-MSI-H any RAS
SAR444245 and pembrolizumab are administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion
Other Name: Keytruda® |
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Experimental: Cohort D2 (Sub-study 04): 3-6L CRC non-MSI-H RAS wild type
SAR444245 is administered every 3 weeks on Day 1 of each cycle (21 days per cycle) and cetuximab is administered on Day 1, Day 8 and Day 15 of each cycle until progressive disease.
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Drug: THOR-707
Solution for infusion: intravenous infusion Drug: Cetuximab Solution for infusion: intravenous infusion
Other Name: Erbitux® |
Primary Outcome Measures :
- Objective Response Rate (ORR) [ Time Frame: Baseline to the date of first documentation of progression, assessed approximatively up to 9 months after the first dose of the last patient ]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 :
- Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Treatment-emergency adverse events (TEAEs) [ Time Frame: From 1st IMP dose up to 30 days after the last dose of IMP ]Incidence 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
- Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Serious Adverse Events (SAEs) [ Time Frame: From 1st IMP dose up to 90 days after the last dose of IMP ]Incidence of 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 [ Time Frame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in ]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 [ Time Frame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in ]Defined as the time from first tumor assessment at which the overall response was recorded as CR or PR 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 [ Time Frame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in ]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 [ Time Frame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in ]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
- Concentrations of SAR444245 [ Time Frame: At Day 1 and Day 2 of Cycle1, at Day 3 and Day 4 of Cycle 1 (only for intensive PK participants), and at Day 1 of Cycle 2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months ]
- Incidence of anti-drug antibodies (ADAs) against SAR444245 [ Time Frame: At Day 1 and Day 8 of Cycle1, at Day 1 of Cycle 2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days) and 30 days after last IMP administration, maximum up to approximately 24 months ]
- Ctrough of infusion of cetuximab [ Time Frame: Day 1 of Cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months ]Concentration observed just after treatment administration during repeated dosing
- Cend of infusion of cetuximab [ Time Frame: Day 1 of Cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participant must be ≥18 years of age (or country's legal age of majority if >18 years), at the time of signing the informed consent.
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Participants with:
- Sub-study01: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic esophageal cancer of the squamous cell carcinoma subtype.
- Sub-study02: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic GC or Siewert Type 2 & 3 GEJ.
- Sub-study03: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic hepatocellular carcinoma (HCC), or clinically by AASLD criteria in cirrhotic patients.
- Sub-study04: Histologically or cytologically confirmed diagnosis of advanced unresectable or mCRC. Only patients with non-MSI-H disease are eligible.
- Participants (all sub-studies) must have at least one measurable lesion.
- Mandatory baseline biopsy for the first 20 participants to enroll in sub-study01, sub-study02 and sub-study04. On-treatment biopsy for at least 20 participants in sub-study04. On-treatment biopsies are otherwise optional per Investigator's discretion for the other cohorts.
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Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees:
- to use approved contraception method and submit to regular pregnancy testing prior to treatment and for at least 120 days (for Cohort A, B1, B2, B3, C, and D1) or 60 days (for Cohort D2) [corresponding to the time needed to eliminate any study intervention(s)].
- and to refrain from donating or cryopreserving eggs for 120 days after discontinuing study treatment.
- Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 3 days [corresponding to time needed to eliminate SAR444245] after the last dose of SAR444245.
- Capable of giving signed informed consent.
Exclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of ≥2.
- Poor organ function.
- Active brain metastases or leptomeningeal disease.
- History of allogenic or solid organ transplant.
- Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery within 28 days prior to first IMP administration.
- 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).
- Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP.
- Severe or unstable cardiac condition within 6 months prior to starting study treatment.
- Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years.
- Participants with baseline SpO2 ≤92% (without oxygen therapy). - Participant has received prior IL2-based anticancer treatment.
- Participants on sub-study02 cohort B1 and B2 or sub-study 04 - cohort D1 with prior treatment with an agent that blocks the PD-1/PD-L1 pathway.
- Receipt of a live-virus or live attenuated-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05104567
Locations
Show 40 study locations
Sponsors and Collaborators
Sanofi
Merck Sharp & Dohme LLC
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT05104567 |
| Other Study ID Numbers: |
ACT16902 U1111-1251-4981 ( Registry Identifier: ICTRP ) 2021-002181-41 ( EudraCT Number ) Merck MK3475-B78 ( Other Identifier: Merck Sharp & Dohme Corp. ) |
| First Posted: | November 3, 2021 Key Record Dates |
| Last Update Posted: | February 15, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| 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 |
Additional relevant MeSH terms:
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Carcinoma Gastrointestinal Neoplasms Squamous Cell Carcinoma of Head and Neck Esophageal Squamous Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases |
Gastrointestinal Diseases Carcinoma, Squamous Cell Neoplasms, Squamous Cell Head and Neck Neoplasms Esophageal Neoplasms Esophageal Diseases Pembrolizumab Cetuximab Antineoplastic Agents, Immunological Antineoplastic Agents |