Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

NCT03324113 | Completed Phase 1

• 2 other identifiers: TCD15054U1111-1191-5464
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

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.

Conditions

Neoplasm Malignant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Treatment emergent adverse events

  Up to an average of 9 months

• Maximum observed concentration (Cmax) of SAR408701

  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

  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)

• Time to reach maximum concentration (Tmax) of SAR408701

  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)

• Tmax of DM4 and Me-DM4

  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)

Study Arms (1)

SAR408701 Monotherapy

EXPERIMENTAL

SAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors

Drug: SAR408701; Drug: dexamethasone; Drug: naphazoline; Drug: diphenhydramine

Interventions

SAR408701 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: Tusamitamab ravtansine

SAR408701 Monotherapy

dexamethasone DRUG

Pharmaceutical form: solution for eye drop Route of administration: eye drop

Also known as: Santeson ophthalmic solution

SAR408701 Monotherapy

naphazoline DRUG

Pharmaceutical form: solution for eye drop Route of administration: eye drop

Also known as: Clearine

SAR408701 Monotherapy

diphenhydramine DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: Restamin Kowa

SAR408701 Monotherapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced or metastatic solid malignant tumor disease for which, in the judgement of the investigator, no standard alternative therapy is available.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (3)

Investigational Site Number : 3920002

Nagoya, Aichi-ken, 464-8681, Japan

Location

Investigational Site Number : 3920003

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Investigational Site Number : 3920001

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Related Publications (1)

• Muro K, Yamazaki K, Kadowaki S, Mishima S, Kawakami T, Tanaka T, Tada K, Fagniez N, Ohshima S, Yoshino T. Phase 1 study evaluating safety and pharmacokinetics of tusamitamab ravtansine monotherapy in Japanese patients with advanced malignant solid tumors. Int J Clin Oncol. 2025 Aug;30(8):1522-1536. doi: 10.1007/s10147-025-02784-4. Epub 2025 May 25.

  PMID: 40413667 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

tusamitamab ravtansine; Dexamethasone; Naphazoline; Diphenhydramine

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 27, 2017
• Study Start: October 17, 2017
• Primary Completion: November 18, 2022
• Study Completion: December 26, 2022
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

JP (3)