CMG901 (sonesitatug vedotin/AZD0901) improved overall survival in the global Phase III CLARITY-Gastric01 trial for CLDN18.2-positive advanced gastric cancer.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Lepu Biopharma has reported positive top-line results from the global Phase III CLARITY-Gastric01 trial (NCT06346392) evaluating CMG901 (sonesitatug vedotin, also known as AZD0901), an investigational Claudin 18.2 (CLDN18.2)-targeted antibody-drug conjugate (ADC) licensed globally to AstraZeneca. The study met its primary overall survival (OS) endpoint in patients receiving third-line or later treatment and also demonstrated a statistically significant and clinically meaningful OS benefit across the broader second-line and later (2L+) population.
The findings represent an important advance for patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and oesophageal adenocarcinoma (EAC) whose tumors express CLDN18.2. Current treatment options after disease progression remain limited, and survival outcomes in later treatment lines are generally poor.
CLDN18.2 Remains an Important Target in Gastric Cancer
CMG901 is an antibody-drug conjugate composed of a CLDN18.2-specific monoclonal antibody linked to the cytotoxic payload monomethyl auristatin E (MMAE) through a cleavable linker. CLDN18.2 is highly expressed in several gastrointestinal malignancies, particularly gastric cancer, while showing limited expression in normal tissues, making it an attractive therapeutic target.
The therapy was the first CLDN18.2-targeted ADC to receive Investigational New Drug (IND) clearance in both China and the United States. It has also received Breakthrough Therapy designation from China’s National Medical Products Administration for advanced gastric cancer and Orphan Drug and Fast Track designations from the US Food and Drug Administration for relapsed or refractory gastric cancer and GEJ adenocarcinoma.
Phase III Trial Demonstrated Clinically Meaningful Survival Benefit
CLARITY-Gastric01 is a randomized, open-label, sponsor-blinded, multicenter Phase III trial conducted across 175 centers in 19 countries. The study enrolled patients with locally advanced or metastatic gastric cancer, GEJ cancer, or EAC whose tumors expressed CLDN18.2 in at least 25% of cells at any staining intensity.
The trial evaluated two dual primary endpoints:
- Overall survival in the third-line and later (3L+) population.
- Progression-free survival (PFS), assessed by blinded independent central review, in the overall second-line and later (2L+) population.
CMG901 achieved the primary OS endpoint in the 3L+ population and met the key secondary endpoint of overall survival in the broader 2L+ population, demonstrating statistically significant and clinically meaningful improvements compared with investigator’s choice of therapy.
Although the study showed a trend toward improved progression-free survival in the 2L+ population, the PFS endpoint did not reach statistical significance.
Safety findings were consistent with previous studies. Investigators reported that CMG901 was well tolerated, with no new safety signals identified.
AstraZeneca Continues Broad Development Program
CMG901 originated through KYM Biosciences, a joint venture between Lepu Biopharma and Keymed Biosciences. Under a 2023 global licensing agreement, AstraZeneca obtained exclusive worldwide rights to develop and commercialize the therapy.
The development program continues to expand beyond CLARITY-Gastric01. Ongoing studies include the Phase III CLARITY-Gastric02 trial evaluating CMG901 with capecitabine, with or without rilvegostomig, as first-line treatment for CLDN18.2-positive, HER2-negative gastric and gastroesophageal cancers. Additional Phase II studies are investigating the ADC in perioperative gastroesophageal cancer and other CLDN18.2-expressing solid tumors, including pancreatic and biliary tract cancers.
Future Development
The positive Phase III results position CMG901 as a potential new treatment option for patients with previously treated CLDN18.2-positive gastric and gastroesophageal cancers, a population with substantial unmet medical need. Detailed efficacy and safety data are expected to be presented at a future scientific meeting and could support regulatory submissions in major global markets as AstraZeneca advances the program toward commercialization.
Reference
POSITIVE TOP-LINE RESULTS ACHIEVED FROM CLARITY-GASTRIC01 GLOBAL PHASE III TRIAL OF CMG901 (AZD0901)
About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.