A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05104567
• Other study ID #: ACT16902
• Secondary ID: U1111-1251-4981M
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 9, 2021
• Est. completion date: September 10, 2024

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 138
• Est. completion date: September 10, 2024
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• 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.

• 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.

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Cancer
• Esophageal Squamous Cell Carcinoma
• Gastric Cancer
• Gastrointestinal Neoplasms
• Hepatocellular Carcinoma
• Oesophageal Adenocarcinoma
• Oesophageal Squamous Cell Carcinoma

Intervention

Drug:
• THOR-707
Solution for infusion: intravenous infusion
• Pembrolizumab
Solution for infusion: intravenous infusion
• Cetuximab
Solution for infusion: intravenous infusion

Locations

Country	Name	City	State
Belgium	Investigational Site Number : 0560002	Bruxelles
Belgium	Investigational Site Number : 0560003	Edegem
Belgium	Investigational Site Number : 0560001	Leuven
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
China	Investigational Site Number : 1560002	Wuhan
France	Investigational Site Number : 2500004	Bordeaux
France	Investigational Site Number : 2500006	Brest
France	Investigational Site Number : 2500002	Paris
France	Investigational Site Number : 2500005	Poitiers
France	Investigational Site Number : 2500001	Villejuif
Italy	Investigational Site Number : 3800002	Milano
Italy	Investigational Site Number : 3800003	Milano
Italy	Investigational Site Number : 3800001	Rozzano	Lombardia
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100004	Seoul	Seoul-teukbyeolsi
Netherlands	Investigational Site Number : 5280001	Amsterdam
Netherlands	Investigational Site Number : 5280003	Rotterdam
Spain	Investigational Site Number : 7240002	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240006	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240101	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240003	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240004	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240001	Pamplona	Navarra
Spain	Investigational Site Number : 7240005	Santander	Cantabria
United States	City of Hope Site Number : 8400007	Duarte	California
United States	AdventHealth Orlando Site Number : 8400005	Orlando	Florida
United States	Seattle Cancer Care Alliance Site Number : 8400009	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Chile,  China,  France,  Italy,  Korea, Republic of,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline to the date of first documentation of progression, assessed approximatively up to 9 months after the first dose of the last patient
Secondary	Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Treatment-emergency adverse events (TEAEs)	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	From 1st IMP dose up to 30 days after the last dose of IMP
Secondary	Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Serious Adverse Events (SAEs)	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	From 1st IMP dose up to 90 days after the last dose of IMP
Secondary	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.	Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
Secondary	Duration of response	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.	Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
Secondary	Clinical benefit rate	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)	Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
Secondary	Progression-free survival	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	Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
Secondary	Concentrations of SAR444245		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
Secondary	Incidence of anti-drug antibodies (ADAs) against SAR444245		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
Secondary	Ctrough of infusion of cetuximab	Concentration observed just after treatment administration during repeated dosing	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
Secondary	Cend of infusion of cetuximab		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