Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

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

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).

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.