Akeso said the first patient has been enrolled in COMPASSION-37, a global, multicenter Phase III trial comparing cadonilimab plus chemotherapy with chemotherapy with or without nivolumab as a first-line treatment for patients with HER2-negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, the company said. The study is a head-to-head design.
The trial is intended to assess the efficacy and safety of cadonilimab as a first-line therapy for advanced gastric cancer in patients from different regions and ethnic backgrounds, and to examine whether blocking both PD-1 and CTLA-4 can improve outcomes beyond the current standard of care. It is co-led by Dr. Yelena Y. Janjigian, chief of the gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center; Professor Markus Möhler of Johannes Gutenberg University Mainz; Professor Jiafu Ji, director of the gastrointestinal cancer center at Peking University Cancer Hospital & Institute; and Professor Lin Shen, director of the department of gastrointestinal oncology at Peking University Cancer Hospital.
Dr. Janjigian, the global principal investigator for the study, said immunotherapy has changed the treatment of stomach and esophagus cancers and that the trial aims to better understand whether cadonilimab can improve outcomes and support longer-term survival. She was previously lead principal investigator for CheckMate 649, and she, Professor Möhler and Professor Shen were investigators on that trial, which Akeso said established nivolumab plus chemotherapy as a standard first-line option.
Chemotherapy with or without a PD-1 inhibitor remains the international standard of care for advanced gastric cancer, but the disease varies in its biology and clinical behavior. In the U.S., first-line PD-1 inhibitor indications in advanced gastric cancer are limited to PD-L1-positive patients, and NCCN and ESMO guidelines preferentially recommend nivolumab-based regimens for patients with a PD-L1 CPS of 5 or higher, which Akeso said leaves effective immunotherapy options for PD-L1-low disease an unmet need. Akeso also cited COMPASSION-15, a randomized, double-blind, placebo-controlled Phase III study of 610 patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma, in which cadonilimab plus chemotherapy reduced the risk of death compared with the control group regardless of PD-L1 expression status; 49.8% of those patients had low PD-L1 expression and 23% had PD-L1-negative disease.
A separate single-arm Phase II study, NCT07631000, led by Dr. Janjigian at Memorial Sloan Kettering Cancer Center, is enrolling patients in the United States and evaluates cadonilimab with FLOT chemotherapy as perioperative treatment for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma. Cadonilimab is approved in China for first-line gastric cancer, first-line cervical cancer and recurrent or metastatic cervical cancer, and is being evaluated in more than 13 registrational or Phase III trials globally, two of them international multicenter studies, Akeso said.