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

NCT ID: NCT04394624

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2024-10-24

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

Detailed Description

The expected duration of the study intervention for participants may vary, based on progression date ; median expected duration of study per participant is estimated 11 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 4 months for end-of-treatment assessments and safety follow-up visit)

Conditions

Non-small Cell Lung Cancer Metastatic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ramucirumab + SAR408701

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

Group Type: EXPERIMENTAL

SAR408701

Intervention Type: DRUG

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

ramucirumab

Intervention Type: DRUG

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

Ramucirumab + pembrolizumab +SAR408701

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

Group Type: EXPERIMENTAL

SAR408701

Intervention Type: DRUG

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

ramucirumab

Intervention Type: DRUG

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

pembrolizumab

Intervention Type: DRUG

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

Interventions

SAR408701

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

Intervention Type: DRUG

ramucirumab

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

Intervention Type: DRUG

pembrolizumab

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Metastatic disease progression fulfilling both of the following 2 criteria:

1. 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

2. 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

Exclusion Criteria

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.
• Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first administration of study intervention.
• 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
• No more than 1-line previous chemotherapy in metastatic setting
• Prior treatment with ramucirumab or docetaxel
• Prior therapy targeting CEACAM5 or maytansinoid treatment (DM1 or DM4 antibody-drug conjugate)
• Contraindication to use of corticosteroid premedication
• Current therapeutic anticoagulation with warfarin, low-molecular-weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible
• Previous enrollment in this study, current participation in any other clinical study involving an investigational study treatment, or any other type of medical research
• Poor bone marrow, liver or kidney functions
• Urine dipstick or routine analysis indicating proteinuria of 2+ or higher, unless a 24 hour urine collection demonstrates <1000 mg of protein.

Triplet cohort exclusions

• History of active autoimmune disease that has required systemic treatment in the past 2 years.
• History of allogeneic tissue/solid organ transplantation.
• Active infection requiring IV systemic therapy within 2 weeks prior to first study intervention administration or active tuberculosis.
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids.
• Symptomatic herpes zoster within 3 months prior to screening.
• Significant allergies to humanized monoclonal antibodies.
• Any radiation therapy to lung >30 Gy within 6 months of first study intervention administration.
• Has received or will receive a live vaccine within 30 days prior to the first study intervention administration.
• Thyroid-stimulating hormone (TSH) out of normal limits. If TSH is not within normal limits at baseline, the subject may still be eligible if T3 and free T4 are within the normal limits

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Henry Ford Hospital Site Number : 8400005

Detroit, Michigan, United States

Roswell Park Cancer Institute Site Number : 8400003

Buffalo, New York, United States

McClinton Cancer Center Site Number : 8400002

Waco, Texas, United States

Investigational Site Number : 1000001

Plovdiv, , Bulgaria

Investigational Site Number : 2030001

Ostrava - Vitkovice, , Czechia

Investigational Site Number : 2030002

Prague, , Czechia

Investigational Site Number : 6200001

Porto, , Portugal

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 7240001

Barcelona / Sabadell, Catalunya [Cataluña], Spain

Investigational Site Number : 7240005

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7240004

Madrid, , Spain

Investigational Site Number : 7240003

Zaragoza, , Spain

Countries

United States; Bulgaria; Czechia; Portugal; South Korea; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1244-1585

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-003914-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT16525

Identifier Type: -

Identifier Source: org_study_id