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Completed

NCT Number: NCT05104567

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

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).

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Key information

Conditions

Oesophageal Squamous Cell Carcinoma Adenocarcinoma Adenocarcinoma Of Esophagus Carcinoma Carcinoma, Hepatocellular Carcinoma, Squamous Cell Colonic Diseases Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Esophageal Squamous Cell Carcinoma Gastric Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Hepatocellular Carcinoma Intestinal Diseases Intestinal Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Squamous Cell Oesophageal Adenocarcinoma Rectal Diseases Stomach Diseases Stomach Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Investigational Site Number : 0560002, Brussels, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

THOR-707

Drug

Solution for infusion: intravenous infusion

Other names: Pegenzileukin

Pembrolizumab

Drug

Solution for infusion: intravenous infusion

Other names: KEYTRUDA®

Cetuximab

Drug

Solution for infusion: intravenous infusion

Other names: ERBITUX®

Primary outcomes

  1. 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

    ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 millimeter (mm) (<1 centimeter [cm]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  2. Cohorts B1, B2 and B3: Objective Response Rate

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 25 months

    ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  3. Cohort C: Objective Response Rate

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 20 months

    ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  4. Cohorts D1 and D2: Objective Response Rate

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months

    ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Secondary outcomes

  1. All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

    Time frame: From first dose of study treatment administration (Day 1) up to 30 days post last dose of study treatment administration, up to approximately 9 months (Cohorts A, D1 and D2), 26 months (Cohorts B1, B2 and B3) and 21 months (Cohort C)

    An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion) or became serious during the TE period.

  2. All Cohorts: Time to Response (TTR)

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

    TTR was defined as the time from the date of first study treatment administration to the first tumor assessment at which the overall response was recorded as PR or CR that was subsequently confirmed as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  3. All Cohorts: Duration of Response (DOR)

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

    DOR was defined as the time from the date of first tumor assessment at which the overall response was recorded as CR or PR that was subsequently confirmed to the date of first documentation of objective PD before the initiation of any post-treatment anti-cancer therapy or death due to any cause, whichever occurred first, as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).

  4. All Cohorts: Clinical Benefit Rate (CBR)

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

    CBR was defined as the percentage of participants with clinical benefit (confirmed CR or PR as best overall response [BOR], or SD lasting at least 6 months), as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to <10 mm (<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. BOR was defined as the best response recorded from the start of the study treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  5. All Cohorts: Progression-Free Survival (PFS)

    Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

    PFS was defined as the time from the date of first study treatment to the date of the first documentation of objective PD or death due to any cause, whichever occurred first, as per RECIST v 1.1. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).

  6. Maximum Concentration Observed (Cmax) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of Cmax of pegenzileukin. The pharmacokinetic (PK) parameters were calculated using non-compartmental method.

  7. Last Concentration Observed Above the Lower Limit of Quantification (Clast) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of Clast of pegenzileukin. The PK parameters were calculated using non-compartmental method.

  8. Time of the Last Concentration Observed Above the Lower Limit of Quantification (Tlast) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of tlast of pegenzileukin. The PK parameters were calculated using non-compartmental method.

  9. Area Under the Plasma Concentration Versus Time Curve Calculated Using the Trapezoidal Method From Time Zero to Tlast (AUClast) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of AUClast of pegenzileukin. The PK parameters were calculated using non-compartmental method.

  10. Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUC) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of AUC of pegenzileukin. The PK parameters were calculated using non-compartmental method.

  11. Observed Accumulation Ratio (Rac) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of Rac of pegenzileukin. Rac was calculated as AUC at Cycle 4 Day 1/AUC at Cycle 1 Day 1. The PK parameters were calculated using non-compartmental method.

  12. Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of Pegenzileukin

    Time frame: Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of Rac,cmax of pegenzileukin. Rac,cmax was calculated as Cmax at Cycle 4 Day 1/Cmax at Cycle 1 Day 1. The PK parameters were calculated using non-compartmental method.

  13. Cohort D2: Concentration Observed Just Before Intervention Administration During Repeated Dosing (Ctrough) of Cetuximab

    Time frame: Cycles 1, 2, 3, 4, 6 and 8 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of Ctrough of Cetuximab. The PK parameters were calculated using non-compartmental method.

  14. Cohort D2: Concentration at End of Infusion (Ceoi) of Cetuximab

    Time frame: Cycles 1, 2, 3, 4, 6 and 8 (each cycle is 21 days)

    Blood samples were collected at specified timepoints for the assessment of Ceoi of Cetuximab. The PK parameters were calculated using non-compartmental method.

  15. All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin

    Time frame: From first dose of study treatment administration (Day 1) up to 30 days post last dose of study treatment administration, up to approximately 9 months (Cohorts A, D1 and D2), 26 months (Cohorts B1, B2 and B3) and 21 months (Cohort C)

    Blood samples were collected at specified timepoints to assess the presence of ADA against pegenzileukin. Treatment-emergent ADA was defined as at least one treatment-induced or treatment-boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA is presented.

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Nov 3, 2021
Registry last updated
Sep 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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