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

Sanofi

Status and phase: Terminated; Phase 2

Conditions: Adenocarcinoma Gastric; Gastrooesophageal Cancer

Treatments: Drug: Tusamitamab ravtansine (SAR408701); Drug: Ramucirumab (CYRAMZA®)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05071053

ACT16444

U1111-1266-5040 (Registry Identifier)

2021-001967-26 (EudraCT Number)

Details and patient eligibility

About

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

Full 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).

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Tusamitamab ravtansine+Ramucirumab

Experimental group

Description:

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.

Treatment:

Drug: Ramucirumab (CYRAMZA®)

Drug: Tusamitamab ravtansine (SAR408701)