Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Pretreated Participants With Gastric Cancer (CARMEN-GC01)

Open-label Study of Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Participants Previously Treated for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma With CEACAM5-positive Tumors

Primary Objectives:

Part 1: to confirm the recommended tusamitamab ravtansine loading dose Q2W in combination with ramucirumab in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma population

Part 2: to assess the antitumor activity of tusamitamab ravtansine loading dose Q2W in combination with ramucirumab in advanced gastric or GEJ adenocarcinoma

Secondary Objectives:

• To assess safety and tolerability
• To assess durability of response (DOR)
• To assess progression-free survival (PFS)
• To assess the disease control rate (DCR)
• To assess the pharmacokinetics (PK)
• To assess the immunogenicity

Study Overview

• Status: Terminated
• Conditions: Adenocarcinoma Gastric; Gastrooesophageal Cancer
• Intervention / Treatment: Drug: Ramucirumab (CYRAMZA®); Drug: Tusamitamab ravtansine (SAR408701)

Detailed Description

34 weeks (up to 4 weeks for screening, a median of 18 weeks for treatment, and a median of 12 weeks for end-of-treatment assessments and the safety follow-up visit).

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, BE-1200
    • Investigational Site Number : 0560002
  • Edegem, Belgium, 2650
    • Investigational Site Number : 0560003
  • Leuven, Belgium, 3000
    • Investigational Site Number : 0560001
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Investigational Site Number : 3920002
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-0280
      • Investigational Site Number : 3920004
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 003-0804
      • Investigational Site Number : 3920001
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Investigational Site Number : 3920003
• Korea, Republic of
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080
      • Investigational Site Number : 4100002
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 05505
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03722
      • Investigational Site Number : 4100003
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 135-710
      • Investigational Site Number : 4100004
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Investigational Site Number : 6430001
  • Saint- Petersburg
    • Pushkin, Saint- Petersburg, Saint- Petersburg, Russian Federation, 196603
      • Investigational Site Number : 6430003
• Spain
  • Granada, Spain, 18014
    • Investigational Site Number : 7240004
  • Madrid, Spain, 28040
    • Investigational Site Number : 7240001
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240002
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Investigational Site Number : 7240003
• Turkey
  • Ankara, Turkey, 06200
    • Investigational Site Number : 7920003
  • Istanbul, Turkey, 34300
    • Investigational Site Number : 7920001
  • Istanbul, Turkey, 34722
    • Investigational Site Number : 7920002
  • Malatya, Turkey
    • Investigational Site Number : 7920004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of gastric or GEJ adenocarcinoma
• Metastatic disease or locally advanced, unresectable disease
• Participants who have measurable target lesion
• Participants with high carcinoembryonic antigen-related cell adhesion molecule (CEACAM5) expression as per central assessment on tumor biospsy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Female participant who agrees to use effective contraceptive methods during and for at least 7 months after the last dose of treatment administration
• Male participant who agrees to use effective contraception methods during and for at least 4 months after the last dose of treatment administration
• Signed informed consent

Exclusion Criteria:

• Untreated brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression
• Significant concomitant illness
• History within the last 3 years of an invasive malignancy other than that treated in this study
• Known uncontrolled infection
• Nonresolution of any prior treatment-related toxicity
• Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy
• Use of contact lenses
• Radiographic evidence of major airway or blood vessel invasion or intratumor cavitation
• History of uncontrolled hereditary or acquired thrombotic disorder or history of aneurism
• Major surgery within 28 days prior to Day 1/first IMP infusion; subcutaneous venous access device placement within 7 days prior to Day 1; or postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months
• History of gross hemoptysis (defined as bright red blood or ≥1/2 teaspoon) within 2 months before the first treatment administration
• Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months before the first administration of treatment administration
• Uncontrolled arterial hypertension (systolic ≥150 mmHg or diastolic ≥90 mmHg) despite standard medical management.
• Serious or nonhealing wound, skin ulcer, or bone fracture within 28 days before the first administration of treatment administration
• Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first administration of treatment administration
• Significant bleeding disorders, vasculitis, or Grade 3-4 gastrointestinal (GI) bleeding within 3 months before the first administration of study intervention.
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection Crohn's disease, ulcerative colitis, or chronic diarrhea
• Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CYP3A inhibitor
• Concurrent treatment with any other anticancer therapy
• Prior treatment targeting CEACAM5 or containing maytansinoid DM1 or DM4 or ramucirumab or taxane or targeting VEGF/VEGFR Poor organ function

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tusamitamab ravtansine+Ramucirumab; Participants received ramucirumab 8 milligram/kilogram (mg/kg) via intravenous (IV) infusion followed by tusamitamab ravtansine loading dose at 170 mg/meter square (m^2) via IV infusion on Cycle 1 Day 1 (each cycle was 2 weeks); and then ramucirumab 8 mg/kg via IV infusion followed by tusamitamab ravtansine 100 mg/m^2 via IV infusion at Cycle 2 and every 2 weeks (Q2W) in all subsequent cycles until disease progression, unacceptable adverse event (AE), death, initiation of a new anticancer therapy, or the participant's or investigator's decision to stop the treatment.

Drug: Ramucirumab (CYRAMZA®); Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion; Drug: Tusamitamab ravtansine (SAR408701); Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Study-Drug Related Dose Limiting Toxicities (DLTs)	The following AEs occurred during the first 2 cycles of treatment, unless due to disease progression or to a cause obviously unrelated to study drug, were considered DLTs: Grade 4 neutropenia for 7 or more consecutive days.; Grade 3 to 4 neutropenia complicated by fever (temperature >=38.5 degree Celsius on more than 1 occasion) or microbiologically or radiographically documented infection.; Grade >=3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention.; Grade 4 non-hematologic AE.; Grade >=3 keratopathy. In addition, any other AE that the Investigators and sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.	From Cycle 1 Day 1 to Cycle 2 Day 14; approximately 28 days
Objective Response Rate (ORR)	The ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) determined per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	The DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST v1.1 or death from any cause, whichever occured first. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
Progression-free Survival (PFS)	The PFS was defined as the time from the first study drug administration to the date of the first documented disease progression or death due to any cause, whichever came first as per RECIST v1.1.	Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
Disease Control Rate (DCR)	The DCR was defined as the percentage of participants who achieved confirmed CR, confirmed PR or stable disease (SD) as per RECIST v1.1. The SD was defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
Individual Observed Predose Concentrations (Ctrough) of Tusamitamab Ravtansine	Blood samples were collected for the measurement of Ctrough of tusamitamab ravtansine.	Pre-infusion on Cycle 2 Day 1
Individual Observed Predose Concentrations (Ctrough) of Ramucirumab	Blood samples were collected for the measurement of Ctrough of concentrations of ramucirumab.	Pre-infusion on Cycle 2 Day 1
Number of Participants With Antitherapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine	Blood samples were collected to assess the presence of ATA against tusamitamab ravtansine in plasma from all participants. ATA incidence was defined as the number of participants found to have seroconverted (treatment-induced ATAs) or boosted their pre-existing ATA response (treatment-boosted ATAs) at any time after first study drug administration.	Upto 92.1 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A SAE was defined as any untoward medical occurrence that, at any dose: resulted in death or was life-threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent disability/incapacity or congenital anomaly/birth defect. TEAE was defined as AEs that developed, worsened, or became serious during the treatment-emergent period.	From the first study drug administration (Day 1) up to 30 days after the last study drug administration, approximately 120 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): November 5, 2024

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 7, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ramucirumab; Maytansine
• Other Study ID Numbers: ACT16444; U1111-1266-5040 (Registry Identifier: ICTRP); 2021-001967-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No