tusamitamab ravtansine monotherapy and in combination in patients with ceacam5-positive advanced solid tumors

Conditions: Breast Cancer Metastatic; Pancreatic Carcinoma Metastatic

Summary: 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

the expected duration of study intervention for participants may vary, based on progression date and the cohort; median expected duration of study per participant is estimated at 8 months for cohort a/c and 6 months for cohort b (up to 1 month for screening, a median of 4 or 2 months for treatment in cohort a/c and cohort b respectively, a median of 1 month for eot, and follow-up visit 90 days after the last imp administration).

Eligibility criteria:
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.