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

Purpose

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

Conditions

  • Breast Cancer Metastatic
  • Pancreatic Carcinoma Metastatic

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A metastatic breast cancer (mBC)
tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)
  • Drug: tusamitamab ravtansine
    Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion
    Other names:
    • SAR408701
Experimental
Cohort B metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)
  • Drug: tusamitamab ravtansine
    Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion
    Other names:
    • SAR408701
Experimental
Cohort C Metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)
  • Drug: tusamitamab ravtansine
    Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion
    Other names:
    • SAR408701
  • Drug: Gemcitabine
    Pharmaceutical form: Lyophilized powder for reconstitution or as a solution for infusion; Route of administration: IV infusion

More Details

Status
Active, not recruiting
Sponsor
Sanofi

Study Contact

Detailed Description

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).