Clinical trial NCT03324113: Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors
Official title: A Phase I Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy in Japanese Patients With Advanced Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Malignant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-10-27
Enrollment: 34
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: IMP-related dose limiting toxicities (DLT)
timeFrame: 4 weeks, Dose escalation q3w part: 3 weeks
Secondary outcomes:
measure: Treatment emergent adverse events
timeFrame: Up to an average of 9 months
measure: Maximum observed concentration (Cmax) of SAR408701
timeFrame: 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)
measure: Cmax of DM4 and Me-DM4
timeFrame: 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)
measure: Time to reach maximum concentration (Tmax) of SAR408701
timeFrame: 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)
measure: Tmax of DM4 and Me-DM4
timeFrame: 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)
measure: Area under the concentration-time curve (AUC) of SAR408701
timeFrame: 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)
measure: AUC of DM4 and Me-DM4
timeFrame: 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)
measure: Assessment of PDy effect
timeFrame: Up to an average of 10 months
measure: Assessment of anti-tumor activity
timeFrame: Up to an average of 10 months
measure: Detection of anti-SAR408701 antibody
timeFrame: Up to an average of 10 months
Other outcomes:
Locations:
city: Kashiwa-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Sunto-Gun
country: Japan
facility: Investigational Site Number 3920001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: