A novel chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising activity in patients with advanced clear cell renal cell carcinoma, offering new hope for those who have exhausted standard treatment options. The investigational therapy ALLO-316 achieved a 33% confirmed objective response rate in patients whose tumors expressed CD70 in at least 50% of cells, according to results from the ongoing TRAVERSE study presented at the 2025 ASCO Annual Meeting.
Addressing Critical Treatment Gap
For patients with metastatic clear cell renal cell carcinoma who did not benefit from checkpoint and tyrosine kinase inhibitors, limited alternative treatment options are available. ALLO-316 represents a novel approach designed to recognize and kill cells expressing CD70, a protein that is elevated in clear cell renal cell carcinoma.
First-in-Human Trial Results
The TRAVERSE study, conducted by Samer Ali Srour, MBChB, MS, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues from other institutions, represents the first clinical evaluation of ALLO-316 in humans. The trial enrolled patients with advanced or metastatic clear cell renal cell carcinoma who had previously failed standard therapies.
A total of 44 patients underwent lymphodepletion as part of the treatment protocol, with 39 patients ultimately receiving one infusion of ALLO-316. The therapy's efficacy was particularly notable in the subset of patients whose tumors showed high CD70 expression, achieving the 33% confirmed objective response rate in those with CD70 present in at least 50% of tumor cells.
Safety and Tolerability Profile
The safety analysis revealed a manageable toxicity profile for this novel CAR T-cell approach. Dose-limiting toxicities were reported in only 2 patients out of the 39 who received treatment. Overall, 42 patients experienced treatment-emergent adverse events, which is consistent with expectations for CAR T-cell therapies.
Cytokine-release syndrome, a known complication of CAR T-cell treatments, developed in 25 patients. Notably, no cases of graft-versus-host disease were observed throughout the study, which is particularly significant given the allogeneic nature of this therapy.
Ongoing Investigation
The TRAVERSE trial continues to enroll and follow patients, with researchers having previously presented data on objective response rates and disease control rates. The ongoing nature of the study suggests that additional safety and efficacy data will become available as patient follow-up continues and enrollment expands.
The results represent an important step forward in expanding treatment options for patients with advanced clear cell renal cell carcinoma, particularly those who have limited alternatives after failing checkpoint inhibitors and tyrosine kinase inhibitors. The CD70-targeting approach offers a novel mechanism of action that could potentially fill a critical gap in the current treatment landscape for this challenging malignancy.
