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) (CARMEN-LC05)

Brief description of study

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

The expected duration of the study intervention for participants may vary based on progression date; median expected duration of study per participant is estimated 10 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months for end-of-treatment assessments and safety follow-up visit).

Clinical Study Identifier: NCT04524689

You may be eligible for this study if you meet the following criteria:

  • Conditions: Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
  • Age: 18 Years
  • Gender: Male or Female

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.

Last updated on 18 May 2022

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