▎WuXi AppTec Content Team Report

Today (October 16), the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China has just announced,M9140 Injection, a Class 1 new drug applied by Merck KGaA, has obtained tacit clinical trial approval. According to the announcement, M9140 is aAnti-CEACAM5 Antibody-Drug Conjugate (ADC), This approval in China is for a Phase 1, open-label study planned to be conducted in Chinese subjects with advanced solid tumors.

Screenshot source:CDE Official Website

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5) is a cell surface protein with limited expression in healthy adult tissues but is highly expressed in various adenocarcinomas, particularly in colorectal cancer patients.。

Public information shows,M9140 is an ADC targeting CEACAM5, with a topoisomerase 1 (TOP1) inhibitor payload exatecan.Preclinical studies have shown that M9140 can specifically bind to CEACAM5 and selectively kill target-positive cancer cells.M9140It also has a strong bystander effect, indicating its potential to treat tumors with heterogeneous target expression. In two CRC PDX models where maytansine-based CEACAM5-targeting ADCs were ineffective, the TOP1 inhibitor-based ADC M9140 demonstrated strong anti-tumor efficacy, reducing tumor volume by 74% and 88%.

In May 2024, the first-in-human trial results of M9140 in patients with metastatic colorectal cancer were selected for oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting. The study evaluated the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 as a monotherapy for colorectal cancer patients who had received two or more prior lines of treatment.

As of the data cutoff date, 40 patients from the United States, the European Union, and Japan have received treatment with M9140 at seven dose levels, with 15 patients still continuing treatment. Efficacy data show: partial response in four patients; stable disease in 17 patients, including six patients with sustained conditions for ≥100 days, and progressive disease in six patients. The best overall response could not be evaluated in 13 patients, including six who had not yet undergone tumor assessment during treatment. The preliminary median progression-free survival was 6.7 months.

The first-in-human Phase 1 clinical study of M9140 for advanced solid tumors is currently underway internationally.. The approval of this product for clinical use in China means that it will also conduct clinical research in China.

References:

[1] Official website of the Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Oct 16, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2]Abstract 2362: Preclinical efficacy and safety of M9140, a novel antibody-drug conjugate (ADC) with topoisomerase 1 (TOP1) inhibitor payload targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)-expressing colorectal tumors. Retrieved Mar 22，2024, From https://aacrjournals.org/cancerres/article/84/6_Supplement/2362/738805/Abstract-2362-Preclinical-efficacy-and-safety-of