Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

Sanofi34 enrolled

Overview

Primary Objective: * To evaluate tolerability and safety of SAR408701 when administered as a single agent according to the investigational medicinal product (IMP) related dose limiting toxicities (DLTs) to determine the recommended dose (RD) of SAR408701 in Japanese patients with advanced malignant solid tumors. Secondary Objectives: * To characterize the overall safety profile of SAR408701 monotherapy. * To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites. * To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for main dose escalation part. * To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria and other indicators of antitumor activity. * To assess the potential immunogenicity of SAR408701.

The study duration per participant will include a period to assess eligibility (screening period) of up to approximately 4 weeks (28 days), a treatment period and an End-of-Treatment (EOT) visit around 30 days after the last administration of IMP, and at least one follow-up (FU) visit after the EOT visit.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasm Malignant

Eligibility

Sex: ALLMin age: 20 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria: * Locally advanced or metastatic solid malignant tumor disease for which, in the judgement of the investigator, no standard alternative therapy is available. * Inclusion is likely to be expressing CEACAM5. * At least 6 x 5 μm slides from formalin-fixed paraffin-embedded (FFPE) archival tissue should be available for retrospective central evaluation of CEACAM5 expression. * Patient understands and has signed the Written Informed Consent form and is willing and able to comply with the requirements of the trial. Exclusion criteria: * Patient less than 20 years old. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2. * Life expectancy \<12 weeks. * Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis. * Female patients of childbearing potential and male patients with female partners of childbearing potential who do not agree to use accepted and effective method of contraception during the study treatment period and for 6 months following discontinuation of IMP. * Significant concomitant illnesses, including all severe medical conditions which, in the opinion of the Investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results. * Prior therapy targeting CEACAM5. * Prior maytansinoid treatments (maytansinoid derivative 1 \[DM1\] or maytansinoid derivative 4 \[DM4\] antibody drug conjugates). * Previous history and or unresolved corneal disorders. * Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by cytochrome P450 (CYP) 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 first administration of SAR408701. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Outcomes

Primary Outcomes

IMP-related dose limiting toxicities (DLT)

IMP-related DLTs are defined as adverse events (AE) related to the IMPs in absence of clear evidence to the contrary, after validation by the Study Committee, and if not related to a disease progression, graded using National Cancer Institute common Toxicity Criteria (NCI-CTC) scale v4.03

Time frame: 4 weeks, Dose escalation q3w part: 3 weeks

Secondary Outcomes

Treatment emergent adverse events

Overall safety profile characterized in terms of the type, frequency, severity, seriousness, and relationship to study therapy of any AEs based on standard and systematic assessment including physical findings, laboratory tests or other investigations

Time frame: Up to an average of 9 months

Maximum observed concentration (Cmax) of SAR408701

Cmax for SAR408701 will be assessed after single and repeat doses, as relevant

Time frame: Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)

Cmax of DM4 and Me-DM4

Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant

Time to reach maximum concentration (Tmax) of SAR408701

Tmax for SAR408701 will be assessed after single and repeat doses, as relevant

Tmax of DM4 and Me-DM4

Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant

Area under the concentration-time curve (AUC) of SAR408701

AUC of SAR408701 from time zero extrapolated to infinity

AUC of DM4 and Me-DM4

AUC of DM4 and Me-DM4 from time zero extrapolated to infinity

Assessment of PDy effect

Assessment of plasma CEACAM5 levels in main dose-escalation part

Time frame: Up to an average of 10 months

Assessment of anti-tumor activity

Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria

Time frame: Up to an average of 10 months

Detection of anti-SAR408701 antibody

Immunogenicity evaluation for anti-SAR408701 antibodies

Time frame: Up to an average of 10 months

Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes