Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04)

NCT04394624 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: ACT16525U1111-1244-15852019-003914-15
• Study Type: interventional
• Target: 31
• Locations: 6 countries
• Sites: 13

Brief Summary

Primary Objectives: Doublet Cohort Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of tusamitamab ravtansine in combination with ramucirumab in the NSQ NSCLC population. Part 2: To assess the antitumor activity of tusamitamab ravtansine in combination with ramucirumab in the NSQ NSCLC population. Triplet cohort To assess the tolerability and to confirm the recommended dose of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab in the NSQ NSCLC population. Secondary Objectives: Doublet Cohort To assess the safety and tolerability of tusamitamab ravtansine in combination with ramucirumab. To assess the durability of the response to treatment with tusamitamab ravtansine in combination with ramucirumab. To assess anti-tumor activity of tusamitamab ravtansine in combination with ramucirumab on progression free survival (PFS) and disease control rate (DCR). To assess the pharmacokinetic (PK) profiles of tusamitamab ravtansine (SAR408701) and ramucirumab when given in combination. To assess the immunogenicity of tusamitamab ravtansine (SAR408701) when given in combination with ramucirumab. Triplet cohort To assess the safety and tolerability of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab To assess the antitumor activity of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab in the NSQ NSCLC population. To assess the immunogenicity of tusamitamab ravtansine when given in combination with ramucirumab and pembrolizumab

Conditions

Non-small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (3)

• Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT)

  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. • Grade \>=3 thrombocytopenia. • Elevated urine protein \>=3 gram(g)/24 hour. • Grade 4 non-hematologic AE. • Grade \>=3 keratopathy. • Grade 4 or refractory hypertension. 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 up to Cycle 2 Day 14, approximately 28 days

• Doublet Cohort - Part 2: Objective Response Rate (ORR)

  The ORR is 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 is defined as disappearance of all target lesions. The PR is 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, and every 8 weeks +/-7 days thereafter, approximately 130 weeks

• Triplet Cohort: Number of Participants With Study Drug-Related Dose-Limiting Toxicity

  The following AEs occurred during the first cycle 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. • Grade \>=3 thrombocytopenia. • Elevated urine protein \>=3 g/24 hour. • Grade 4 non-hematologic AE. • Grade \>=3 keratopathy. • Grade 4 or refractory hypertension. In addition, any other AE that the Investigators and sponsor deemed dose limiting, regardless of its grade, was also considered as DLT.

  From Cycle 1 Day 1 up to Cycle 1 Day 21

Secondary Outcomes (16)

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

  From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks

• Number of Participants With Potentially Clinically Significant Abnormalities: Hematology

  From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks

• Number of Participants With Potentially Clinically Significant Abnormalities: Metabolism

  From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks

• Number of Participants With Potentially Clinically Significant Abnormalities: Electrolytes

  From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks

• Number of Participants With Potentially Clinically Significant Abnormalities: Renal Function

  From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks

Study Arms (2)

Ramucirumab + SAR408701

EXPERIMENTAL

Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks.

Drug: SAR408701; Drug: ramucirumab

Ramucirumab + pembrolizumab +SAR408701

EXPERIMENTAL

Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination

Drug: SAR408701; Drug: ramucirumab; Drug: pembrolizumab

Interventions

SAR408701 DRUG

Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion

Ramucirumab + SAR408701; Ramucirumab + pembrolizumab +SAR408701

ramucirumab DRUG

Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion

Ramucirumab + SAR408701; Ramucirumab + pembrolizumab +SAR408701

pembrolizumab DRUG

Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion

Ramucirumab + pembrolizumab +SAR408701

Eligibility Criteria

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

You may qualify if:

• Metastatic disease progression fulfilling both of the following 2 criteria:
• Having progressive disease during or after platinum-based chemotherapy (at least 2 cycles). Maintenance therapy following platinum-based chemotherapy is not considered as a separate regimen. Adjuvant/neoadjuvant treatment for a patient who had a relapse with metastatic disease during or within 6 months of completing treatment will be considered as first-line treatment.
• AND
• Having progressive disease during or after 1 immune checkpoint inhibitor (anti-PD1/PD-L1); this could be given as monotherapy or in combination with platinum-based chemotherapy (whatever the order).
• Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5 expression of ≥2+ in archival tumor sample (or if not available, fresh biopsy sample) involving at least 50 % of the tumor cell population as demonstrated prospectively by central laboratory via immune histochemistry (IHC).
• At least one measurable lesion by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• A female participant who agrees to use effective contraceptive methods during and for at least 7 months after the last dose of study intervention.
• A male participant who agrees to use effective contraception methods during and for at least 4 months after the last dose of study intervention
• Signed informed consent

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Patients with untreated brain metastases and history of leptomeningeal disease.
• Significant concomitant illnesses that would impair the patient's participation in the study or interpretation of the results.
• History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• Non-resolution of any prior treatment related toxicity to \< grade 2 according to NCI CTCAE V5.0, except for alopecia, vitiligo and active thyroiditis controlled with hormonal replacement therapy
• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis
• Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted.
• Radiographic evidence of major airway or blood vessel invasion or intratumor cavitation
• History of uncontrolled hereditary or acquired arterial thrombotic disorder or history of aneurism.
• Major surgery within 28 days prior to Day 1/first IMP infusion,. Postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months.
• History of gross hemoptysis within 2 months before the first administration of study intervention.
• Clinically relevant congestive heart failure (CHF; NYHA II-IV, or LVEF less than 50%) or symptomatic or poorly controlled cardiac arrhythmia.
• Any arterial thrombotic event within 6 months before the first administration of study intervention.
• 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 study intervention.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

Henry Ford Hospital Site Number : 8400005

Detroit, Michigan, 48202, United States

Location

Roswell Park Cancer Institute Site Number : 8400003

Buffalo, New York, 14263, United States

Location

McClinton Cancer Center Site Number : 8400002

Waco, Texas, 76712, United States

Location

Investigational Site Number : 1000001

Plovdiv, 4004, Bulgaria

Location

Investigational Site Number : 2030001

Ostrava - Vitkovice, 703 84, Czechia

Location

Investigational Site Number : 2030002

Prague, 12808, Czechia

Location

Investigational Site Number : 6200001

Porto, 4200-162, Portugal

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 7240001

Barcelona / Sabadell, Catalunya [Cataluña], 08208, Spain

Location

Investigational Site Number : 7240005

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 7240004

Madrid, 28040, Spain

Location

Investigational Site Number : 7240003

Zaragoza, 50009, Spain

Location

MeSH Terms

Interventions

tusamitamab ravtansine; Ramucirumab; pembrolizumab

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 prematurely terminated due to the discontinuation of the overall development of tusamitamab ravtansine (SAR408701) by the sponsor. The decision was 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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: May 19, 2020
• Study Start: August 31, 2020
• Primary Completion: March 6, 2023
• Study Completion: October 24, 2024
• Last Updated: June 6, 2025
• Results First Posted: March 28, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

BU (1); PT (1); US (3); CZ (2); KR (2); ES (4)