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

NCT05071053 | Terminated Phase 2 Results

• 3 other identifiers: ACT16444U1111-1266-50402021-001967-26
• Study Type: interventional
• Target: 35
• Locations: 6 countries
• Sites: 21

Brief Summary

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

Conditions

Adenocarcinoma Gastric; Gastrooesophageal Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  From the first study drug administration (Day 1) up to 30 days after the last study drug administration, approximately 120 weeks

• Duration of Response (DOR)

  Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks

• Progression-free Survival (PFS)

  Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks

• Disease Control Rate (DCR)

  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

  Pre-infusion on Cycle 2 Day 1

Study Arms (1)

Tusamitamab ravtansine+Ramucirumab

EXPERIMENTAL

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®); Drug: Tusamitamab ravtansine (SAR408701)

Interventions

Ramucirumab (CYRAMZA®) DRUG

Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion

Tusamitamab ravtansine+Ramucirumab

Tusamitamab ravtansine (SAR408701) DRUG

Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion

Tusamitamab ravtansine+Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (21)

Investigational Site Number : 0560002

Brussels, BE-1200, Belgium

Location

Investigational Site Number : 0560003

Edegem, 2650, Belgium

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number : 3920002

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Investigational Site Number : 3920004

Matsuyama, Ehime, 791-0280, Japan

Location

Investigational Site Number : 3920001

Sapporo, Hokkaido, 003-0804, Japan

Location

Investigational Site Number : 3920003

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Investigational Site Number : 6430003

Pushkin, Saint- Petersburg, Sankt-Peterburg, 196603, Russia

Location

Investigational Site Number : 6430001

Arkhangelsk, 163045, Russia

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 05505, South Korea

Location

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, 135-710, South Korea

Location

Investigational Site Number : 7240002

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240003

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number : 7240004

Granada, 18014, Spain

Location

Investigational Site Number : 7240001

Madrid, 28040, Spain

Location

Investigational Site Number : 7920003

Ankara, 06200, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Istanbul, 34300, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Istanbul, 34722, Turkey (Türkiye)

Location

Investigational Site Number : 7920004

Malatya, Turkey (Türkiye)

Location

MeSH Terms

Interventions

Ramucirumab; tusamitamab ravtansine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated as per Sponsor decision and not related to any safety concern.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 7, 2021
• Study Start: November 16, 2021
• Primary Completion: June 23, 2023
• Study Completion: November 5, 2024
• Last Updated: August 22, 2025
• Results First Posted: December 5, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

BE (3); TU (4); KR (4); JP (4); ES (4); RU (2)