ALLO-316 Produces Responses in Heavily Pretreated Clear Cell Renal Carcinoma

The allogeneic CD70 CAR T-cell agent ALLO-316 was safe and displayed significant activity in heavily-pretreated patients with advanced or metastatic CD70-postive clear cell renal cell carcinoma (RCC), according to data from the phase 1 TRAVERSE trial (NCT04696731) 2025 ASCO Annual Meeting.¹

Updated findings from TRAVERSE revealed that the overall response rate (ORR) per RECIST 1.1 criteria among efficacy-evaluable patients treated in phase 1b (n = 20) of the study was 25%. Notably, the ORR in patients with a CD70 tumor positive score (TPS) of at least 50% (n = 16) was 31%. All efficacy-evaluable patients treated to date in the study (n = 38) experienced an ORR of 21%; those with a CD70 TPS of at least 50% (n = 31) experienced an ORR of 26%. No patients with a CD70 TPS below 50% in either phase 1b or the overall population experienced a response.

“A single dose of ALLO-316 demonstrated a 31% confirmed ORR in patients with heavily pretreated advanced or metastatic clear cell RCC,” the study authors wrote in the presentation. “Four of five responses are ongoing, including one extending beyond a year after treatment, representing a potential breakthrough for CAR T-[cell] therapy in [patients with] solid tumors.”

In October 2024, the FDA granted regenerative medicine advanced therapy (RMAT) designation to ALLO-316 for the treatment of patients with CD70-positive advanced or metastatic RCC.² The RMAT designation was based on prior data from TRAVERSE.

Unpacking the TRAVERSE Study Design

TRAVERSE enrolled patients who were at least 18 years old with advanced or metastatic clear cell RCC.¹ Patients needed to have experienced disease progression following treatment with PD-1 axis and VEGF-targeted therapies. Eligible patients also needed to have CD70-positive disease by immunohistochemistry, an ECOG performance status of 0 or 1, and adequate, pulmonary, cardiac, renal, hepatic, and hematologic function.

In phase 1b, patients received standard lymphodepletion with fludarabine 30 mg/m² and cyclophosphamide 500 mg/m² daily for 3 days. ALLO-316 was then administered via a single dose of 80 x 10⁶ CAR-positive cells. Patients were then followed for 60 months.

The primary end point was in phase 1b was the rate of treatment-emergent adverse effects (TEAEs). Secondary end points included ORR, complete response rate, duration of response, time to response, progression-free survival, overall survival, and CAR T expansion kinetics.

At baseline, the median ages among patients treated in phase 1b and those in the overall population were 56 years (range, 35-67) and 60 (range, 35-70), respectively. Most patients in both groups were male (91% vs 88%), underwent prior nephrectomy (100% vs 90%), and had IMDC intermediate risk disease (64% vs 54%). Patients in both groups received a median of 4 (range, 1-11) prior lines of therapy. Prior therapies in both groups included anti–PD-L1 therapy (100% vs 100%), anti–CTLA-4 therapy (55% vs 62%), cabozantinib (Cabometyx; 82% vs 78%), at least 2 prior TKIs (82% vs 64%), at least 3 prior TKIs (59% vs 34%), and an mTOR inhibitor (68% vs 40%).

Additional Efficacy Data and Safety Results

Additional findings from TRAVERSE demonstrated that patients with a CD70 TPS of at least 50% treated in phase 1b achieved a greater than 30% reduction in the diameter of baseline target lesions at a rate of 44%.

In terms of safety, any-grade TEAEs were reported in 100% of patients treated in phase 1b. The most common any-grade TEAEs included neutropenia (68%), decreased white blood cell count (68%), anemia (59%), and thrombocytopenia (55%). These TEAEs occurred at grade 3 or higher severity at respective rates of 68%, 68%, 41%, and 27%. Notably, there were no treatment-related grade 5 adverse effects.

“[Our] results underscore the transformative potential of allogeneic CAR T-[cell therapy] in [patients with] solid tumors and validate further development of ALLO-316 in RCC and other CD70-positive malignancies,” the study authors wrote in their conclusion.

References

1. Srour SA, Chahoud J, Drakaki A, et al. ALLO-316 in advanced clear cell renal cell carcinoma (ccRCC): updated results from the phase 1 TRAVERSE study. J Clin Oncol. 2025;43(suppl 16):4508. doi: 10.1200/JCO.2025.43.16_suppl.4508
2. Allogene Therapeutics receives FDA regenerative medicine advanced therapy (RMAT) designation for ALLO-316, an AlloCAR T™ investigational product for adult patients with advanced or metastatic renal cell carcinoma (RCC). News release. Allogene Therapeutics. October 29, 2024. Accessed June 25, 2025. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-receives-fda-regenerative-medicine