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

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05104567

Collaborator

Merck Sharp & Dohme LLC (Industry)

280

Enrollment

Locations

Arms

25.5

Anticipated Duration (Months)

7.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

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 A; B1,B2, B3, C and D1} = 735 days or until PD ], 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 Design

Study Type:

Interventional

Anticipated 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 :

Dec 9, 2021

Anticipated Primary Completion Date :

Jan 22, 2024

Anticipated Study Completion Date :

Jan 23, 2024

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion Other Names: Keytruda®
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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion Other Names: Keytruda®
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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion Other Names: Keytruda®
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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion Other Names: Keytruda®
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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion Other Names: 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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Pembrolizumab Solution for infusion: intravenous infusion Other Names: Keytruda®
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.	Drug: THOR-707 Solution for infusion: intravenous infusion Drug: Cetuximab Solution for infusion: intravenous infusion Other Names: Erbitux®

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [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) [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) [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 [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 [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 [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 [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 [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 [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 [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 [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope-Site Number:8400007	Duarte	California	United States	91010
2	Advent Health Medical Group - West Florida-Site Number:8400005	Tampa	Florida	United States	33614
3	Massachusetts General Hospital-Site Number:8400008	Boston	Massachusetts	United States	02114
4	Columbia University Medical Center-Site Number:8400003	New York	New York	United States	10032
5	Seattle Cancer Care Alliance-Site Number:8400009	Seattle	Washington	United States	98115
6	Investigational Site Number :0560002	Bruxelles		Belgium	BE-1200
7	Investigational Site Number :0560003	Edegem		Belgium	2650
8	Investigational Site Number :0560001	Leuven		Belgium	3000
9	Investigational Site Number :1520001	Santiago	Reg Metropolitana De Santiago	Chile	8420383
10	Investigational Site Number :1560001	Beijing		China	100021
11	Investigational Site Number :1560002	Wuhan		China	430022
12	Investigational Site Number :2500004	Bordeaux		France	33075
13	Investigational Site Number :2500006	Brest		France	29200
14	Investigational Site Number :2500003	Nantes		France	44093
15	Investigational Site Number :2500002	Paris		France	75015
16	Investigational Site Number :2500005	Poitiers		France	86021
17	Investigational Site Number :2500001	Villejuif		France	94800
18	Investigational Site Number :2760001	Mainz		Germany	55131
19	Investigational Site Number :3800001	Rozzano	Milano	Italy	20089
20	Investigational Site Number :3800003	Milano		Italy	20132
21	Investigational Site Number :3800002	Milano		Italy	20133
22	Investigational Site Number :3800006	Roma		Italy	00168
23	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03080
24	Investigational Site Number :4100004	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03722
25	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi	Korea, Republic of	05505
26	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi	Korea, Republic of	06351
27	Investigational Site Number :5280001	Amsterdam		Netherlands	1118 HV
28	Investigational Site Number :5280003	Rotterdam		Netherlands	3015 GD
29	Investigational Site Number :6160003	Rzeszow	Podkarpackie	Poland	35-055
30	Investigational Site Number :7240002	Barcelona	Barcelona [Barcelona]	Spain	08035
31	Investigational Site Number :7240006	Barcelona	Barcelona [Barcelona]	Spain	08036
32	Investigational Site Number :7240005	Santander	Cantabria	Spain	39008
33	Investigational Site Number :7240003	Madrid / Madrid	Madrid, Comunidad De	Spain	28007
34	Investigational Site Number :7240004	Madrid / Madrid	Madrid, Comunidad De	Spain	28050
35	Investigational Site Number :7240101	Madrid	Madrid, Comunidad De	Spain	28027
36	Investigational Site Number :7240001	Pamplona	Navarra	Spain	31008

Sponsors and Collaborators

Sanofi
Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT05104567

Other Study ID Numbers:

ACT16902
U1111-1251-4981
2021-002181-41
Merck MK3475-B78

First Posted:

Nov 3, 2021

Last Update Posted:

Aug 3, 2022

Last Verified:

Aug 2, 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

Gastrointestinal Neoplasms

Squamous Cell Carcinoma of Head and Neck

Esophageal Squamous Cell Carcinoma

Pembrolizumab

Cetuximab

Study Results

No Results Posted as of Aug 3, 2022