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
- Conditions
- metastatic breast cancermetastatic pancreatic adenocarcinoma10027476
- Registration Number
- NL-OMON51893
- Lead Sponsor
- Genzyme Europe BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
- Participant must be at least 18 years of age.
- Participants with at least one measurable lesion according to the RECIST 1.1
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 CEACAM5 by centrally assessed IHC assay.
Cohort A:
- 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.
Cohort B:
- Have confirmed diagnosis of pancreatic ductal adenocarcinoma.
- 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:
- Have confirmed diagnosis of pancreatic ductal adenocarcinoma.
- 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.
- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies.
- Capable of giving signed informed consent.
Medical Condition
- 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 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.
Prior/Concomitant therapy
- Concurrent treatment with any other anti-cancer therapy.
- Washout period before the first administration of study intervention of less
than 3 weeks of 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 3 weeks of the first study
intervention administration.
- Any previous systemic therapy with taxane or gemcitabine (for Cohort C only).
Prior/concurrent clinical study experience
- 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.
Diagnostic assessments
- Poor renal function.
- Poor hepatic function.
- Poor bone marrow function.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Cohort A, B and C part 2: objective Response Rate (ORR) of tusamitamab<br /><br>ravtansine (SAR408701) of participants who have a confirmed complete response<br /><br>(CR) or partial response (PR).<br /><br>- Cohort C part 1: Incidence of dose-limiting toxicites (DLTs) in the 28 Day<br /><br>DLT observation period (Cycle 1)</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Incidence of participants with treatment-emergent adverse events (TEAEs),<br /><br>serious adverse events (SAEs) and laboratory abnormalities according to the<br /><br>National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events<br /><br>(CTCAE) v5.0.<br /><br>- Progression-free survival (PFS).<br /><br>- Disease control rate (DCR).<br /><br>- Duration of response (DOR).<br /><br>- Incidence of participants with anti-therapeutic antibodies (ATAs) against<br /><br>tusamitamab ravtansine (SAR408701).<br /><br>- Pharmacokinetic parameters of tusamitamab ravtansine and gemcitabine</p><br>