M-9140 (Precemtabart Tocentecan): An Investigational CEACAM5-Targeting Antibody-Drug Conjugate for Advanced Solid Tumors

I. Executive Summary

M-9140, also identified as precemtabart tocentecan, is an investigational antibody-drug conjugate (ADC) engineered by Merck KGaA, Darmstadt, Germany. It represents the first ADC developed utilizing the company's proprietary technology platform. M-9140 is designed to selectively target the Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5), a glycoprotein frequently overexpressed on the surface of various solid tumors, including colorectal, pancreatic, and gastric cancers, while exhibiting limited expression in normal tissues. The therapeutic strategy of M-9140 involves the targeted delivery of a potent cytotoxic payload, exatecan (a topoisomerase I inhibitor), directly to CEACAM5-expressing cancer cells. Upon binding and internalization, exatecan is released, inducing DNA damage and subsequent tumor cell apoptosis.

Currently, M-9140 is undergoing Phase 1/2 clinical evaluation across multiple studies. The cornerstone trial, NCT05464030 (PROCEADE-CRC-01), has completed its dose-escalation phase and is now in a randomized dose-optimization phase, evaluating doses of 2.4 mg/kg and 2.8 mg/kg administered intravenously every three weeks in patients with heavily pretreated metastatic colorectal cancer (mCRC). Preliminary results from this study have indicated a manageable safety profile, characterized primarily by hematological toxicities. Notably, no interstitial lung disease (ILD) or significant ocular toxicities—adverse events of concern with some other ADCs—have been reported in early clinical findings, aligning with preclinical observations and the drug's specific design features aimed at mitigating such risks. A single Grade 5 sepsis event has been noted, emphasizing the need for careful infection management.