The antibody-drug conjugate M9140 exhibited activity in pretreated patients with advanced colorectal cancer, according to preliminary data from a phase I study presented by Kopetz et al at the 2024 ASCO Annual Meeting (Abstract 3000).
Background
M9140 is one of the first antibody-drug conjugates with a topoisomerase 1 inhibitor payload designed to target the cell surface protein CEACAM5—which is detected in over 90% of colorectal cancers.
“Patients with advanced colorectal cancer typically face a challenging prognosis, so there’s a critical need for new treatment options,” emphasized lead study author Scott Kopetz, MD, PhD, Professor of Gastrointestinal Medical Oncology and Associate Vice President for Translational Integration at The University of Texas MD Anderson Cancer Center, Houston.
Study Methods and Results
In the new study, the researchers assigned 40 pretreated patients with advanced colorectal cancer from across the United States, Europe, and Japan to receive seven different dose levels of M9140. The researchers found that 10% of the patients experienced a partial response and 42.5% of them achieved stable disease. Further, the patients involved in the study experienced a preliminary median progression-free survival of 6.7 months.
The researchers reported that the most common adverse events were hematologic, including neutropenia, thrombocytopenia, and anemia. Notably, there were no instances of interstitial lung disease or ocular toxicity, which are commonly associated with similar antibody-drug conjugates. The data suggest that M9140 has a manageable safety profile at a maximum tolerated dose of 2.8 mg/kg, with recommended doses for further study set at 2.4 and 2.8 mg/kg.
Conclusions
The new findings indicated that M9140 may offer a potential new approach to treating advanced colorectal cancer.
“I’m encouraged by the positive response in many of these patients and eagerly anticipate the results from the ongoing trial,” Dr. Kopetz underscored.
The researchers plan to further evaluate the safety and efficacy of M9140 in a randomized expansion study in order to determine the long-term outcomes.
Disclosure: The research in this study was supported by EMD Serono Research & Development Institute. For full disclosures of the study authors, visit meetings.asco.org.
