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Sponsor: Sanofi
Conditions: Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Interventions: SAR408701 (Tusamitamab ravtansine), Pembrolizumab, Cisplatin, Carboplatin, Pemetrexed
Countries: United States, Brazil, Chile, Czechia, France, Hungary, Israel, Spain
Primary Objective: * Safety run-in part: 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 to be tested in the expansion part of the study in the NSQ NSCLC population * Expansion part (including participants treated at the recommended dose for expansion \[RDE\] from the Safety Run-in part): to assess the antitumor activity of several dose levels (DLs; if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population Secondary Objectives: * To assess the safety and tolerability of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy with pemetrexed in the NSQ NSCLC population * To assess the antitumor activity of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population * To assess the durability of the response to treatment with several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population * To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy 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 a 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
Sex: ALL
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
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 1% 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 * Life expectancy of at least 3 months Exclusion criteria: * Medical condition requiring concomitant administration of a medication with a strong CYP3A 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.
- Westwood, Kansas, United States
- Natal, Rio Grande do Norte, Brazil
- Temuco, La Araucanía, Chile
- Viña del Mar, Valparaiso, Chile
- Santiago, Chile
- Santiago, Chile
- Olomouc, Czechia
- Ostrava - Vitkovice, Czechia
- Avignon, France
- Brest, France
- Pessac, France
- Poitiers, France
- Budapest, Hungary
- Farkasgyepü, Hungary
- Ramat Gan, Israel
- Tel Aviv, Israel
- A Coruña, A Coruña [La Coruña], Spain
- Badalona, Catalunya [Cataluña], Spain
- Oviedo, Principality of Asturias, Spain
- Las Palmas, Spain
- Madrid, Spain
- Madrid, Spain