Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors (CARMEN-BT01)

Sanofi

Status and phase: Active, not recruiting; Phase 2

Conditions: Pancreatic Carcinoma Metastatic; Breast Cancer Metastatic

Treatments: Drug: Gemcitabine; Drug: tusamitamab ravtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04659603

2020-003096-18 (EudraCT Number)

ACT16432

U1111-1244-1644 (Other Identifier)

Details and patient eligibility

About

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

Full 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).

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 3 patient groups

Cohort A metastatic breast cancer (mBC)

Experimental group

Description:

tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)

Treatment:

Drug: tusamitamab ravtansine

Cohort B metastatic pancreatic adenocarcinoma (mPAC)

Experimental group

Description:

tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)

Treatment:

Drug: tusamitamab ravtansine

Cohort C Metastatic pancreatic adenocarcinoma (mPAC)

Experimental group

Description:

tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)

Treatment:

Drug: tusamitamab ravtansine

Drug: Gemcitabine