According to the results of a phase I study reported by Srour et al in the Journal of Clinical Oncology, the investigational allogeneic CD70-targeted chimeric antigen receptor (CAR) T-cell therapy ALLO-316 showed encouraging clinical activity with a manageable safety profile in heavily pretreated patients with advanced clear cell renal cell carcinoma (ccRCC).
Study Details
The TRAVERSE trial was a first-in-human, multicenter, open-label phase Ia/b trial evaluating the safety and preliminary efficacy of ALLO-316 in adults with advanced or metastatic ccRCC. Eligible patients were between 18 and 75 years and had received prior immune checkpoint inhibition and VEGFR-targeted therapy. After an early protocol amendment, enrollment required tumors to express CD70, with expression measured by tumor proportion score (TPS).
A total of 51 patients were enrolled across 10 centers between March 2021 and February 2025, with 50 included in the safety analysis and 46 receiving ALLO-316. Patients had received a median of four prior lines of therapy, and 84% had CD70-positive tumors, including 66% with CD70 TPS ≥ 50%. Phase Ia evaluated escalating doses of ALLO-316 with different lymphodepletion regimens, whereas phase Ib confirmed the selected regimen of fludarabine plus cyclophosphamide followed by a single infusion of 80 × 106 CAR T cells. The primary endpoint was safety, including dose-limiting toxicities.
Key Results
The investigators identified the phase Ib regimen as the optimal balance of safety and activity. Across all treated patients, the objective response rate was 17.4%. In the phase Ib cohort, the objective response rate increased to 25.0%, reaching 31.3% among patients whose tumors had CD70 TPS ≥ 50%. No objective responses were observed in patients with CD70 TPS < 50%. Additionally, 35.0% of evaluable phase Ib patients experienced more than a 30% reduction in target lesion size, and responses generally occurred within 28 days of treatment. At a minimum follow-up of 8 months, no responding patients had experienced disease progression. Median overall survival in phase Ib was 15.2 months.
Grade 3 or higher neutropenia occurred in 62.0% of patients, decreased white blood cell count in 54.0%, and anemia in 36.0%. Cytokine-release syndrome occurred in 62.0% of patients overall, although grade ≥ 3 events were reported in only 2.0%. No grade ≥ 3 immune effector cell–associated neurotoxicity syndrome events or graft-vs-host disease were observed.
The investigators concluded: “ALLO-316 had manageable safety and encouraging antitumor activity in CD70-positive ccRCC. The TRAVERSE trial demonstrates proof of concept for the role of allogeneic CAR T-cell therapy in solid tumors.”
Samer A. Srour, MB ChB, MS, of the Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Allogene Therapeutics, Inc. For full disclosures of the study authors, visit ascopubs.org.
