Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With NSQ NSCLC (CARMEN-LC05)

• Status: Recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

•To assess the tolerability and to determine the recommended doses of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed in the NSQ NSCLC population

Secondary Objectives:

• To assess the safety and tolerability of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed

• To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy, with or without pemetrexed in the NSQ NSCLC population

• To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, pemetrexed, cisplatin, and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine + pembrolizumab) or triplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy) or a quadruplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed)

• To assess the immunogenicity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Carboplatin; Maytansine; Pembrolizumab; Pemetrexed

Criteria

Inclusion criteria :

• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations.

• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease).

• Expression of CEACAM5 as demonstrated prospectively by a centrally assessed Immunohistochemistry (IHC) assay of ≥2+ in intensity involving at least 50% (for Part A and Part B) and at least 1% (for Part C) of the tumor cell population in archival tumor sample (or if not available fresh biopsy sample).

• Measurable disease based on RECIST 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

• Capable of giving signed informed consent

Exclusion criteria:

• Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CTP3A inhibitor.

• Uncontrolled brain metastases and history of leptomeningeal disease.

• Significant concomitant illness, including any severe medical condition that, in the opinion of the investigator or Sponsor, 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.

• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection.

• 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 randomization or active tuberculosis.

• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids

• Non-resolution of any prior treatment-related toxicity to < Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy.

• Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted.

• Symptomatic herpes zoster within 3 months prior to screening.

• Significant allergies to humanized monoclonal antibodies.

• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).

• Concurrent treatment with any other anticancer therapy.

• Have received prior chemotherapy treatment for advanced/metastatic NSCLC.

• The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation

• Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for any investigational treatment).

• Any prior therapy targeting CEACAM5.

• Any prior treatment with any other anti-PD-1, or PD-L1 or programmed death ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4.

• Any prior maytansinoid treatment (DM1 or DM4 ADC).

• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication. Daily steroid replacement therapy or any corticosteroid premedication if applicable are allowed.

• 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.

• Any major surgery within the preceding 3 weeks of the first study intervention administration.

Prior/concurrent clinical study experience

• Current participation in any other clinical study involving an investigational study treatment or any other type of medical research.

• Poor organ function

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