Promising Phase 1 Results of ALLO-316 in Advanced ccRCC Unveiled

The recent presentation by Dr. Samer A. Srour at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting highlighted the encouraging findings from the phase 1 TRAVERSE study of ALLO-316, an innovative allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting advanced clear cell renal cell carcinoma (ccRCC). This groundbreaking study, identified by its clinical trial number NCT04696731, showcased a confirmed objective response rate (ORR) of 25%, which elevated to 31% among patients exhibiting high CD70 expression. Furthermore, some patients demonstrated ongoing durable responses surpassing one year, marking a significant development in treatment options for this challenging malignancy.

Dr. Srour, an associate professor at The University of Texas MD Anderson Cancer Center, provided an overview of the study's background and objectives. The TRAVERSE study is pioneering as the first-in-human trial for ALLO-316, specifically targeting patients with advanced or metastatic ccRCC who have previously failed standard treatments, including checkpoint inhibitors and tyrosine kinase inhibitors.

In the phase 1b cohort, the study enrolled 22 heavily pretreated patients, out of which 20 received the ALLO-316 infusion. The median age of participants was 56 years, with a median of four prior therapy lines attempted. Notably, 59% of patients had undergone three or more tyrosine kinase inhibitor treatments, underscoring the dire need for effective therapies in this patient population.

One of the key advantages of ALLO-316 is its off-the-shelf availability, allowing for swift patient treatment—averaging only four days from enrollment to administration. This rapid turnaround can be crucial for patients with aggressive disease progression, differentiating it from conventional autologous CAR T-cell therapies that require extensive preparation time.

The safety profile of ALLO-316 was deemed manageable, with cytokine release syndrome occurring in 68% of patients, mostly classified as grade 1 or 2. Dr. Srour pointed out that four patients (18%) experienced immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a complication increasingly recognized in CAR T-cell therapies. Importantly, the study employed an algorithm for early detection and management of IEC-HS, which helped mitigate severe adverse events.

The efficacy results, especially the 25% ORR in a heavily pretreated cohort, are particularly noteworthy. The data indicate that most responses were durable, with only one of the five objective responses recorded at follow-up showing disease progression. Dr. Srour emphasized that the unique mechanism of ALLO-316, which allows for depletion of host CD70+ T cells, may enhance CAR T-cell persistence and efficacy, a phenomenon he referred to as the "Dagger effect."

The implications of these promising results extend beyond ccRCC, as the research suggests potential applications in other solid tumors expressing CD70. Dr. Srour expressed optimism about progressing toward a phase 2 registrational study, which could further validate ALLO-316's therapeutic benefit in treating advanced malignancies.

In summary, the TRAVERSE study provides hopeful evidence for the viability of CAR T-cell therapies in solid tumors, particularly in a patient population with limited treatment options. The ongoing development of ALLO-316 could signal a significant advancement in the treatment landscape for ccRCC and potentially other cancers in the near future.