E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced and metastatic gastrointestinal cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061534 |
E.1.2 | Term | Oesophageal squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030137 |
E.1.2 | Term | Oesophageal adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the antitumor activity of SAR444245 in combination with other anticancer therapies |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety of SAR444245 when combined with other anticancer therapies - To assess other indicators of antitumor activity - To assess the pharmacokinetics of SAR444245 when given in combination with other anticancer therapies - To assess the immunogenicity of SAR444245 - Only for sub study 04 – Cohort D2: To assess active concentrations of cetuximab when given in combination with SAR444245 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Sub-study01: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants with advanced and metastatic esophageal squamous cell carcinoma Protocol number: ACT16902-S01, version 01 dated on 2021-08-30 - Sub-study02: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants with advanced and metastatic gastric cancer or gastro-esophageal junction adenocarcinoma Protocol number: ACT16902-S02, version 01 dated on 2021-08-30 - Sub-study03: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants with advanced and metastatic hepatocellular carcinoma Protocol number: ACT16902-S03, version 01 dated on 2021-08-30 - Sub-study04: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab or cetuximab for the treatment of participants with advanced and metastatic colorectal cancer Protocol number: ACT16902-S04, version 01 dated on 2021-08-30
For related objectives, refer to E.2.1 and E.2.2. |
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E.3 | Principal 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 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 |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: - 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. pathway. - Receipt of a live or live attenuated-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to the date of first documentation of progression, assessed approximatively up to 9 months after the first dose |
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E.5.2 | Secondary end point(s) |
1- Assessment of SAR444245 safety profile when combined with other anti-cancer therapies 2- Time to response 3- Duration of response 4- Clinical benefit rate 5- Progression-free survival 6- Concentrations of SAR444245 7- Incidence of anti-drug antibodies (ADAs) against SAR444245 8- Ctrough of infusion of cetuximab 9- Cend of infusion of cetuximab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1:SAE:from 1st IMP dose up to 90 days after the last dose of IMP AE/TEAE:from 1st IMP dose up to 30 days after the last dose of IMP 2to5:Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in 6: 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 7: 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 8-9: D 1 of Cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 7 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
China |
Korea, Republic of |
United States |
France |
Poland |
Netherlands |
Spain |
Germany |
Italy |
Belgium |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 16 |