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

Gastrooesophageal Cancer Clinical Trial

— CARMEN-GC01  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05071053
• Other study ID #: ACT16444
• Secondary ID: U1111-1266-50402
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 16, 2021
• Est. completion date: June 28, 2024

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 - To assess durability - To assess progression-free survival (PFS) - To assess the disease control rate (DCR) - To assess the pharmacokinetics (PK) - To assess the immunogenicity

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 34
• Est. completion date: June 28, 2024
• Est. primary completion date: June 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma Gastric
• Gastrooesophageal Cancer

Intervention

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

Locations

Country	Name	City	State
Belgium	Investigational Site Number : 0560002	Bruxelles
Belgium	Investigational Site Number : 0560003	Edegem
Belgium	Investigational Site Number : 0560001	Leuven
Japan	Investigational Site Number : 3920002	Kashiwa-shi	Chiba
Japan	Investigational Site Number : 3920004	Matsuyama-shi	Ehime
Japan	Investigational Site Number : 3920001	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920003	Sunto-gun	Shizuoka
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100004	Seoul	Seoul-teukbyeolsi
Russian Federation	Investigational Site Number : 6430001	Arkhangelsk
Russian Federation	Investigational Site Number : 6430003	Pushkin, Saint- Petersburg	Saint- Petersburg
Spain	Investigational Site Number : 7240002	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Granada
Spain	Investigational Site Number : 7240001	Madrid
Turkey	Investigational Site Number : 7920003	Ankara
Turkey	Investigational Site Number : 7920001	Istanbul
Turkey	Investigational Site Number : 7920002	Istanbul
Turkey	Investigational Site Number : 7920004	Malatya

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Belgium,  Japan,  Korea, Republic of,  Russian Federation,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of study drug related dose-limiting toxicities (DLTs)	Part 1: Number of participants with DLTs	Cycle 1 Day 1 to Cycle 2 Day 14 (approximatively 1 month)
Primary	Objective Response Rate	Part 2: Objective Response Rate (ORR), defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	From baseline up to approximately 24 months
Secondary	Incidence of Adverse Events	Number of participants with adverse events	From baseline up to approximately 24 months
Secondary	Duration of Response	Duration of response (DOR), defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST 1.1 or death from any cause, whichever occurs first	From baseline up to approximately 24 months
Secondary	Progression-free survival	Progression-free survival, defined as the time from the first investigational medicinal product (IMP) administration to the date of the first documented disease progression or death due to any cause, whichever comes first	From baseline up to approximately 24 months
Secondary	Disease control rate	Disease control rate, defined as the proportion of participants with confirmed CR or PR or SD as BOR per RECIST 1.1	From baseline up to approximately 24 months
Secondary	Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine	Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine	From baseline up to approximately 24 months