Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

Neoplasm Malignant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03324113
• Other study ID #: TCD15054
• Secondary ID: U1111-1191-5464
• Status: Completed
• Phase: Phase 1
• Start date: October 17, 2017
• Est. completion date: December 26, 2022

Study information

• Verified date: January 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 26, 2022
• Est. primary completion date: November 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasm Malignant
• Neoplasms

Intervention

Drug:
• SAR408701
Pharmaceutical form: solution for infusion Route of administration: intravenous
• dexamethasone
Pharmaceutical form: solution for eye drop Route of administration: eye drop
• naphazoline
Pharmaceutical form: solution for eye drop Route of administration: eye drop
• diphenhydramine
Pharmaceutical form: tablet Route of administration: oral

Locations

Country	Name	City	State
Japan	Investigational Site Number 3920003	Kashiwa-Shi
Japan	Investigational Site Number 3920002	Nagoya-Shi
Japan	Investigational Site Number 3920001	Sunto-Gun

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	4 weeks, Dose escalation q3w part: 3 weeks
Secondary	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	Up to an average of 9 months
Secondary	Maximum observed concentration (Cmax) of SAR408701	Cmax for SAR408701 will be assessed after single and repeat doses, as relevant	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)
Secondary	Cmax of DM4 and Me-DM4	Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant	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)
Secondary	Time to reach maximum concentration (Tmax) of SAR408701	Tmax for SAR408701 will be assessed after single and repeat doses, as relevant	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)
Secondary	Tmax of DM4 and Me-DM4	Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant	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)
Secondary	Area under the concentration-time curve (AUC) of SAR408701	AUC of SAR408701 from time zero extrapolated to infinity	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)
Secondary	AUC of DM4 and Me-DM4	AUC of DM4 and Me-DM4 from time zero extrapolated to infinity	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)
Secondary	Assessment of PDy effect	Assessment of plasma CEACAM5 levels in main dose-escalation part	Up to an average of 10 months
Secondary	Assessment of anti-tumor activity	Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria	Up to an average of 10 months
Secondary	Detection of anti-SAR408701 antibody	Immunogenicity evaluation for anti-SAR408701 antibodies	Up to an average of 10 months