Phase 1 study evaluating safety and pharmacokinetics of tusamitamab ravtansine monotherapy in Japanese patients with advanced malignant solid tumors

TL;DR

This study evaluated the safety and drug levels of tusamitamab ravtansine in Japanese patients with advanced solid tumors, finding it generally well-tolerated with no severe dose-limiting side effects.

Contribution

The study provides new safety and pharmacokinetic data for tusamitamab ravtansine in Japanese patients with advanced solid tumors.

Findings

Tusamitamab ravtansine showed a manageable safety profile with no dose-limiting toxicities in most patients.

Drug exposure increased proportionally with dose in the range of 80–170 mg/m².

The best overall response was stable disease, with no confirmed tumor shrinkage observed.

Abstract

Tusamitamab ravtansine (SAR408701) is an immunoconjugate that binds carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and delivers its cytotoxic payload to target cells. Here, we report findings from three dosing regimens of tusamitamab ravtansine administration in Japanese adults with advanced malignant solid tumors.

Japanese adults (aged ≥ 20 years) with CEACAM5-expressing malignant solid tumors were enrolled in this Phase 1, open-label, non-randomized, dose-escalation evaluation of tusamitamab ravtansine in three parts: (i) main dose-escalation part with every two weeks (Q2W) administration, (ii) loading dose (LD) part with Q2W administration with a LD at Cycle 1 (C1) only, and (iii) dose-escalation every three weeks (Q3W) part. Primary objectives were to evaluate the tolerability and safety of tusamitamab ravtansine.

Nine patients were enrolled in the main dose-escalation part, 16 patients in the dose-escalation bis part with LD, and nine patients in the dose-escalation Q3W part. Administration of tusamitamab ravtansine resulted in a manageable safety profile with no dose-limiting toxicities reported during the observation period except for two events during dose-escalation bis Q2W part. Most common adverse events (AEs) were corneal events, gastrointestinal disorders, and metabolic events. After first administration, tusamitamab ravtansine exposure was dose proportional over the dose range 80–170 mg/m2. Best overall response (BOR) was stable disease, observed in all three parts; confirmed response was not observed at any dose level.

Tusamitamab ravtansine demonstrated a tolerable safety profile at a dose of 80–170 mg/m2 in three different administration schedules in Japanese adults with metastatic solid tumors.

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