Dr Srour on the Safety and Efficacy of the Allogeneic CAR T-Cell Therapy CTX130 in Advanced ccRCC

Samer A. Srour, MB ChB, MS, assistant professor, Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses efficacy and safety of the allogeneic CAR T-cell therapy CTX130, which was evaluated in patients with advanced clear cell renal cell carcinoma (ccRCC) as part of the phase 1 COBALT-RCC trial (NCT04438083).

Updated findings from the study, which were presented at the 2024 AACR Annual Meeting, showed that no dose-limiting toxicities were observed across any of the 4 dose levels administered to patients enrolled on the study (n = 16). Grade 1/2 cytokine release syndrome (CRS) occurred in 50% of patients; however, no grade 3 or higher CRS events were observed. Additionally, no instances of immune effector cell–associated neurotoxicity syndrome (ICANs), graft-vs-host disease, or hemophagocytic lymphohistiocytosis (HLH) were reported. The absence of ICANs and HLH was notable since those toxicities have been commonly associated with CAR T-cell therapies in patients with hematologic malignancies, according to Srour.

Three patients experienced infections that were considered serious, including 1 patient who had grade 5 pneumonia; however, none of these infections were determined to be related to CTX130. Four patients had serious adverse effects related to the CAR T-cell therapy and all were CRS.

Regarding efficacy, 1 patient (6.3%) achieved a complete response (CR) that exceeded 3 years at data cutoff, according to Srour. Although no other responses were reported, 75.0% of patients experienced stable disease (SD), translating to a disease control rate of 81.3%. One patient maintained SD beyond month 12.

Although only 1 response was observed in this cohort of patients, the durable CR serves as a proof of concept for the use of an allogeneic CAR T-cell therapy in patients with ccRCC, Srour explains. Selecting the right target and overcoming the suppressive tumor microenvironment has been a challenge in developing these types of cellular therapies for patients with solid tumors, but the goal remains to continue refining this modality for patients with ccRCC and other histologies, Srour concludes.