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

Part of paid clinical trials in Duarte, California.

Sponsor
Sanofi
Study ID
NCT05104567
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • THOR-707 — DRUG
    Solution for infusion: intravenous infusion
  • Pembrolizumab — DRUG
    Solution for infusion: intravenous infusion
  • Cetuximab — DRUG
    Solution for infusion: intravenous infusion

Study Details

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).

Key Dates

Start date
Dec 9, 2021
Status verified
Sep 2025
Primary completion
Jul 26, 2023
Completion
Sep 9, 2024

Study Design

Enrollment
138 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort A: ESCC Post PD-1/PD-L1; SAR444245 24 mcg/kg + Pembrolizumab as 2/3L Therapy
    Participants with advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC), regardless of programmed cell death-ligand 1 (PD-L1) expression (any combined positive score \[CPS\]), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-programmed cell death-1 (PD-1)/PD-L1 based regimen were included in this cohort. Participants received SAR444245 24 microgram per kilogram (mcg/kg) along with pembrolizumab 200 milligram (mg) via intravenous (IV) infusion every 3 weeks (q3w) on Day 1 of each cycle (each cycle is 21 days) (as second-line or third-line \[2/3L\] therapy), until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.
  • Experimental: Cohort B1: GC/GEJ PD-1/PD-L1 naïve non-MSI-H CPS >=1
    Cohort B1: GC/GEJ PD-1/PD-L1 naïve non-MSI-H CPS \>=1; SAR444245 24mcg/kg+Pembrolizumab as 1-3L Therapy. Participants with advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 \& 3 gastro-esophageal junction adenocarcinoma (GEJ) and for whom standard of care (SOC) was not in best interest or where no SOC was established, non-high-level microsatellite instability (MSI-H) disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \>=1 GC/GEJ were included in this cohort. Participants received SAR444245 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as first to \[1-\]3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
  • Experimental: Cohort B2: GC/GEJ PD-1/PD-L1 naïve non-MSI-H CPS <1
    Cohort B2: GC/GEJ PD-1/PD-L1 naïve non-MSI-H CPS \<1; SAR444245 24 mcg/kg+Pembrolizumab as 1-3L Therapy. Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received SAR444245 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
  • Experimental: Cohort B3: GC/GEJ Post PD-1/PD-L1 non-MSI-H; SAR444245 24 mcg/kg + Pembrolizumab as 2-4L Therapy
    Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received SAR444245 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-fourth \[4\]L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
  • Experimental: Cohort C: HCC Post PD-1/PD-L1; SAR444245 24 mcg/kg + Pembrolizumab as 2/3L Therapy
    Participants with advanced unresectable or metastatic hepatocellular carcinoma (HCC), regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least stable disease (SD) as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received SAR444245 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
  • Experimental: Cohort D1: CRC non-MSI-H any RAS; SAR444245 24 mcg/kg + Pembrolizumab as 3-6L Therapy
    Participants with advanced unresectable or metastatic colorectal cancer (CRC), regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received SAR444245 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-sixth \[6\]L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
  • Experimental: Cohort D2: CRC non-MSI-H RAS Wild Type; SAR444245 24 mcg/kg + Cetuximab as 3-6L Therapy
    Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received SAR444245 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/square meter (m\^2) on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.

Primary Outcome Measure

Cohort A: Objective Response Rate (ORR) [ Time Frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months ]

Locations (3)

FacilityCityStateZIPSite coordinators
City of Hope Site Number : 8400007DuarteCalifornia91010-
AdventHealth Orlando Site Number : 8400005OrlandoFlorida32804-
Seattle Cancer Care Alliance Site Number : 8400009SeattleWashington98115-

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