NEW YORK – Carsgen on Monday said it has completed enrollment of patients with Claudin18.2 (CLDN18.2)-positive advanced gastric and gastroesophageal cancer to a pivotal Phase II trial of its CAR T-cell therapy satricabtagene autoleucel (satri-cel).
The Shanghai-based company is conducting the open-label, randomized trial in China to compare the efficacy and safety of satri-cel against physician's choice of therapy in gastric cancer patients who have failed at least two prior lines of treatment.
According to Carsgen, new treatments for gastric cancer are much needed in China, where there were about 395,000 new cases and approximately 260,000 deaths from the disease in 2022. There are currently no approved therapies targeting CLDN18.2.
In Carsgen's earlier Phase I trial published in Nature Medicine, CLDN18.2-positive gastric or gastroesophageal cancer patients treated with satri-cel had no dose-limiting toxicities, no grade 3 or higher cytokine release syndrome, and no immune effector cell-associated neurotoxicity syndrome. Among 51 patients, 54.9 percent responded to satri-cel. The disease control rate was 96.1 percent, and the median duration of response was 6.4 months. In a separate Phase Ib trial, the overall response rate in the same disease setting was 57.1 percent, and the disease control rate was 78.6 percent.
Carsgen is also evaluating satri-cel with Moderna's off-the-shelf messenger RNA cancer vaccine under an August 2023 agreement. Other than satri-cel, the company is developing a CLDN18.2-targeted monoclonal antibody, dubbed AB011, with Roche's checkpoint inhibitor Tecentriq (atezolizumab) as a first-line treatment for CLDN18.2-positive advanced gastric cancer patients in China.
With satri-cel and AB011, Carsgen joins a growing list of companies investing in developing CLDN18.2-directed treatments. Astellas, for example, is developing zolbetuximab for treating advanced HER2-negative, CLDN18.2-positive gastric cancer, but received a complete response letter from the US Food and Drug Administration in January flagging deficiencies at a third-party manufacturing site. Phanes Therapeutics and Triumvira are also developing CLDN18.2-targeted therapies, a bispecific antibody and an autologous T-cell antigen coupler therapy, respectively.