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

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05071053

Collaborator

(none)

Enrollment

Locations

Arm

16.5

Anticipated Duration (Months)

1.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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
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

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma Gastric Gastrooesophageal Cancer	Drug: Ramucirumab (CYRAMZA®) Drug: Tusamitamab ravtansine (SAR408701)	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

38 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 16, 2021

Anticipated Primary Completion Date :

Jan 20, 2023

Anticipated Study Completion Date :

Apr 3, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tusamitamab ravtansine+Ramucirumab Part 1: participants to receive an intravenous (IV) dose of tusamitamab ravtansine in combination with an IV dose of ramucirumab on Day 1 of Cycle 1 followed by an additional IV dose of tusamitamab in combination with IV dose of ramucirumab at Day 1 Cycle 2 of 14-day cycle in all subsequent cycles. Part 2: participants to receive the recommended dose of tusamitamab ravtansine established in the Part 1 in combination with IV dose of ramucirumab on Day 1 of Cycle 1 followed by IV dose of tusamitamab in combination with IV dose of ramucirumab at Day 1 Cycle 2 of 14-day cycle in all subsequent cycles.	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

Arm

Intervention/Treatment

Experimental: Tusamitamab ravtansine+Ramucirumab

Part 1: participants to receive an intravenous (IV) dose of tusamitamab ravtansine in combination with an IV dose of ramucirumab on Day 1 of Cycle 1 followed by an additional IV dose of tusamitamab in combination with IV dose of ramucirumab at Day 1 Cycle 2 of 14-day cycle in all subsequent cycles. Part 2: participants to receive the recommended dose of tusamitamab ravtansine established in the Part 1 in combination with IV dose of ramucirumab on Day 1 of Cycle 1 followed by IV dose of tusamitamab in combination with IV dose of ramucirumab at Day 1 Cycle 2 of 14-day cycle in all subsequent cycles.

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

Outcome Measures

Primary Outcome Measures

Incidence of study drug related dose-limiting toxicities (DLTs) [Cycle 1 Day 1 to Cycle 2 Day 14 (approximatively 1 month)]
Part 1: Number of participants with DLTs
Objective Response Rate [From baseline up to approximately 24 months]
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

Secondary Outcome Measures

Incidence of Adverse Events [From baseline up to approximately 24 months]
Number of participants with adverse events
Duration of Response [From baseline up to approximately 24 months]
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
Progression-free survival [From baseline up to approximately 24 months]
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
Disease control rate [From baseline up to approximately 24 months]
Disease control rate, defined as the proportion of participants with confirmed CR or PR or SD as BOR per RECIST 1.1
Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine [From baseline up to approximately 24 months]
Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number :0560002	Bruxelles		Belgium	BE-1200
2	Investigational Site Number :0560003	Edegem		Belgium	2650
3	Investigational Site Number :0560001	Leuven		Belgium	3000
4	Investigational Site Number :3920002	Kashiwa-shi	Chiba	Japan	277-8577
5	Investigational Site Number :3920004	Matsuyama-shi	Ehime	Japan	791-0280
6	Investigational Site Number :3920001	Sapporo-shi	Hokkaido	Japan	003-0804
7	Investigational Site Number :3920003	Sunto-gun	Shizuoka	Japan	411-8777
8	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03080
9	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03722
10	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi	Korea, Republic of	05505
11	Investigational Site Number :4100004	Seoul	Seoul-teukbyeolsi	Korea, Republic of	135-710
12	Investigational Site Number :6430001	Arkhangelsk		Russian Federation	163045
13	Investigational Site Number :6430004	Lapino Village		Russian Federation	143030
14	Investigational Site Number :6430002	Moscow		Russian Federation	109089
15	Investigational Site Number :6430003	Pushkin, Saint- Petersburg		Russian Federation	196603
16	Investigational Site Number :7240002	Barcelona	Barcelona [Barcelona]	Spain	08035
17	Investigational Site Number :7240003	Barcelona	Barcelona [Barcelona]	Spain	08036
18	Investigational Site Number :7240004	Granada		Spain	18014
19	Investigational Site Number :7240001	Madrid		Spain	28040
20	Investigational Site Number :7920003	Ankara		Turkey	06200
21	Investigational Site Number :7920001	Istanbul		Turkey	34300
22	Investigational Site Number :7920002	Istanbul		Turkey	34722
23	Investigational Site Number :7920004	Malatya		Turkey

Sponsors and Collaborators

Sanofi

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT05071053

Other Study ID Numbers:

ACT16444
U1111-1266-5040
2021-001967-26

First Posted:

Oct 7, 2021

Last Update Posted:

Aug 3, 2022

Last Verified:

Aug 2, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Adenocarcinoma

Ramucirumab

Maytansine

Study Results

No Results Posted as of Aug 3, 2022