The Center for Drug Evaluation (CDE) in China has issued a draft proposal for “Technical Guidelines for Clinical Trials of Chimeric Antigen Receptor (CAR)-T Cell Therapy for Malignant Tumors of the Lymphatic and Hematological System.” These guidelines are designed to provide a framework for the design, protocol, and execution of clinical trials for CAR-T cell products, which are increasingly significant in the treatment of various cancers.
The draft guidelines are particularly relevant for autologous CAR-T cell products, though they may also extend to allogeneic or universal CAR-T cells and other genetically modified lymphocyte products, such as CAR-NK and TCR-T cells. The malignant tumors targeted primarily include B-ALL, B-NHL, and MM, which have seen a concentration of clinical trials for CAR-T cell products.
Recognizing the potential for adverse reactions such as cytokine release syndrome (CRS) and neurotoxicity, the guidelines emphasize the importance of a sponsor developing a clinical research and development plan that balances the potential benefits and safety risks of CAR-T therapy with disease staging and existing treatment options.
In designing clinical trials, considerations should include subject age, prior treatments, treatment line, and the use of bridging therapy. Efficacy evaluation should prioritize overall survival (OS) as the most significant endpoint, with non-recurrent mortality (NRM) due to treatment-related toxicity also being assessed, given the high safety risks associated with CAR-T therapy. Alternative endpoints encompass overall response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR), progression-free survival (PFS), disease-free survival (DFS), event-free survival (EFS), response duration (DOR), and minimal residual disease (MRD) based on cellular assessment.- Flcube.com
