Clinical trial NCT05104567: A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Oesophageal Squamous Cell Carcinoma
Gastric Cancer
Hepatocellular Carcinoma
Colorectal Cancer
Oesophageal Adenocarcinoma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-11-03
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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 \[max 35 cycles {cohort A; B1,B2, B3, C and D1} = 735 days or until PD {cohort D2}\], 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline to the date of first documentation of progression, assessed approximatively up to 9 months after the first dose of the last patient
Secondary outcomes:
measure: Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Treatment-emergency adverse events (TEAEs)
timeFrame: From 1st IMP dose up to 30 days after the last dose of IMP
measure: Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Serious Adverse Events (SAEs)
timeFrame: From 1st IMP dose up to 90 days after the last dose of IMP
measure: Time to response
timeFrame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
measure: Duration of response
timeFrame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
measure: Clinical benefit rate
timeFrame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
measure: Progression-free survival
timeFrame: Baseline to the date of first documentation of progression, assessed approximatively up to 18 months after the last patient-in
measure: Concentrations of SAR444245
timeFrame: 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
measure: Incidence of anti-drug antibodies (ADAs) against SAR444245
timeFrame: 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
measure: Ctrough of infusion of cetuximab
timeFrame: 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
measure: Cend of infusion of cetuximab
timeFrame: 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
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Site Number : 8400007
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando Site Number : 8400005
state: Florida
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance Site Number : 8400009
state: Washington
city: Bruxelles
country: Belgium
facility: Investigational Site Number : 0560002
city: Edegem
country: Belgium
facility: Investigational Site Number : 0560003
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Wuhan
country: China
facility: Investigational Site Number : 1560002
city: Bordeaux
country: France
facility: Investigational Site Number : 2500004
city: Brest
country: France
facility: Investigational Site Number : 2500006
city: Paris
country: France
facility: Investigational Site Number : 2500002
city: Poitiers
country: France
facility: Investigational Site Number : 2500005
city: Villejuif
country: France
facility: Investigational Site Number : 2500001
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800001
state: Lombardia
city: Milano
country: Italy
facility: Investigational Site Number : 3800003
city: Milano
country: Italy
facility: Investigational Site Number : 3800002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280001
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280003
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240002
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240006
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Investigational Site Number : 7240005
state: Cantabria
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240003
state: Madrid, Comunidad De
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240004
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240101
state: Madrid, Comunidad De
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240001
state: Navarra
Study officials:
References: