Open-label, Multi-cohort, Phase 2 Trial, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine (SAR408701) Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

ACT16432

Primary Objective: * For Cohort A, Cohort B, and Cohort C Part 2: To assess the antitumor activity of tusamitamab ravtansine in metastatic breast cancer (mBC) and tusamitamab ravtansine monotherapy and in combination with gemcitabine in metastatic pancreatic adenocarcinoma (mPAC) * For Cohort C Part 1: Confirmation of the recommended tusamitamab ravtansine dose when administered in combination with gemcitabine Secondary Objectives: * To assess the safety and tolerability of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine * To assess other efficacy parameters of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine * To assess the immunogenicity of tusamitamab ravtansine * To assess the pharmacokinetics (PK) of tusamitamab ravtansine and gemcitabine when given in combination

2021-03-29

2024-08-30

2024-10-01

Active (not recruiting)

Early phase I

50

Inclusion Criteria: * Participant must be at least 18 years of age * Participants with at least one measurable lesion according to the RECIST v1.1 criteria that has not been irradiated (ie, newly arising lesions in previously irradiated areas are accepted). * Participants with ECOG performance status 0 to 1. * Evidence of metastatic disease. * Expression of CEACAM 5 by centrally assessed IHC assay. * Male and female participants willing to comply with contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Cohort A: mBC * Histological or cytologic diagnosis of breast cancer. * Have received at least 2 prior cytotoxic chemotherapy regimens for non-TNBC tumor type or at least 1 for TNBC tumor type but not more than 4 in the locally recurrent or metastatic setting. Cohorts B and C: mPAC - Have confirmed diagnosis of pancreatic ductal adenocarcinoma. Cohort B: mPAC: - Have documented radiographic progression or documented intolerance after at least 1 prior systemic chemotherapy line which included either gemcitabine (or relapsed within 6 months of completion of gemcitabine adjuvant therapy) or a 5-fluorouracil based regimen (including capecitabine) but no more than 2 prior chemotherapy lines for locally advanced/metastatic disease. Cohort C: mPAC - Have documented radiographic progression or documented intolerance after 1st line fluoropyrimidine-containing chemotherapy (or relapsed within 6 months of completion of chemotherapy as adjuvant therapy) for locally advanced/metastatic disease. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * Medical condition requiring concomitant administration of a medication with a narrow therapeutic window, that is metabolized by cytochrome P450 (CYP450), and for which a dose reduction cannot be considered. * Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before the first administration of study intervention. * Life expectancy less than 3 months. * Untreated brain metastases or history of leptomeningeal disease. * Significant concomitant illness * 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 human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or active hepatitis A, B or C infection. * 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 (HRT). * Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. * Use of contact lenses. Participants using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded. * Concurrent treatment with any other anti cancer therapy. * 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 prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy, or any investigational treatment). * Any prior therapy targeting CEACAM5. * Prior maytansinoid DM4 treatment (ADC). * Any major surgery within the preceding 2 weeks of the first study intervention administration. * Previous enrollment in this study or current participation in any other clinical study involving an investigational study treatment or any other type of medical research. * Poor renal function * Poor hepatic function * Poor bone marrow function Cohort C: mPAC - Any previous systemic therapy with taxane or gemcitabine (for Cohort C only). The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

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2024-05-08