A recent phase I clinical trial conducted in China has revealed promising results for CMG901, a first-in-class antibody-drug conjugate targeting claudin 18.2, in the treatment of advanced gastric and gastroesophageal junction (GEJ) cancers. The trial findings, published in The Lancet Oncology by Ruan et al., highlight CMG901’s manageable safety profile and encouraging antitumor activity.
About CMG901
CMG901 combines a humanized claudin 18.2 antibody with monomethyl auristatin E, a microtubule-disrupting agent. This innovative approach targets claudin 18.2, a protein overexpressed in gastric and GEJ cancers, enabling precision in cancer cell destruction while minimizing off-target effects.
Key Findings from the KYM901 Study
The study enrolled 134 patients in two phases: dose-escalation and dose-expansion. During the dose-escalation phase, no maximum tolerated dose was reached, and the recommended phase II dose was identified as 2.2 mg/kg. The dose-expansion phase included 107 patients receiving CMG901 every three weeks.
- Safety Profile: While adverse events were common, they were generally manageable. The most frequent side effects included vomiting, decreased appetite, anemia, and proteinuria. Serious adverse events occurred in 50% of patients, with one treatment-related death reported.
- Efficacy: Among 113 patients treated with the recommended dose, a confirmed objective response was achieved in 28% of cases, with a median response duration of 7.9 months.
Implications for Future Treatment
The results position CMG901 as a potential breakthrough in addressing the unmet needs of patients with advanced gastric and GEJ cancers. Its precision-targeting mechanism not only enhances treatment efficacy but also reduces systemic toxicity.
As the study moves into phase II, CMG901 holds the promise of becoming a transformative option for patients battling these aggressive cancers. With further validation, this novel therapy could redefine the standard of care in advanced gastric and GEJ cancer treatment.
Disclosure: The study was funded by KYM Biosciences. The corresponding authors, Dr. Rui-Hua Xu and Dr. Dong-Sheng Zhang, are affiliated with Sun Yat-sen University Cancer Center, Guangzhou.
References:
- Ruan X, Xu RH, Zhang DS, et al. Phase I study of CMG901, a first-in-class claudin 18.2-targeting antibody-drug conjugate, in advanced gastric and gastroesophageal junction cancers. Lancet Oncol. 2025;26(2):175-187. doi:10.1016/S1470-2045(25)00025-3
- KYM Biosciences. KYM901 trial results demonstrate promising efficacy of CMG901 in claudin 18.2-expressing gastric cancer. News Release. February 2025. Link
- Sun Yat-sen University Cancer Center. Dr. Rui-Hua Xu and Dr. Dong-Sheng Zhang present new data on CMG901 at ASCO GI 2025. Research Update. February 2025. Link
- The Lancet Oncology. Emerging antibody-drug conjugates in gastric cancer: A step forward in targeted therapy. Editorial. Lancet Oncol. 2025;26(2):162-164. doi:10.1016/S1470-2045(25)00030-7