Allogene Therapeutics' ALLO-316, an investigational AlloCAR T product, has received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for adult patients with CD70-positive advanced or metastatic renal cell carcinoma (RCC) who have previously undergone immune checkpoint inhibitor and VEGF-targeting therapy. This designation, announced by Allogene Therapeutics, aims to accelerate the development and review of this potential therapy for a patient population with limited treatment options.
The RMAT designation is reserved for products intended to treat, modify, reverse, or cure serious or life-threatening diseases, with preliminary clinical data suggesting the potential to address unmet medical needs. ALLO-316 had previously been granted fast track designation in March 2022.
Clinical Trial Data Supporting RMAT Designation
The RMAT designation is supported by interim data from the ongoing phase 1 TRAVERSE trial (NCT04696731), initially presented at the American Association of Cancer Research (AACR) Annual Meeting in April 2023. The trial enrolled 19 patients with clear cell RCC, with 18 included in the efficacy analysis. The disease control rate was 89%, and the overall response rate was 17% among all patients.
In a subset of 10 patients with CD70-expressing RCC, the disease control rate reached 100%, and the overall response rate was 30%. The longest response observed lasted 8 months, with a median progression-free survival of 5.0 months in this subset. The data also indicated a correlation between higher baseline tumor CD70 immunohistochemistry H-Score and greater tumor reduction.
Safety Profile
The safety profile of ALLO-316 was generally consistent with that of other autologous CAR T therapies. Adverse events (AEs) of any grade included neurotoxicity (68%), cytokine release syndrome (CRS; 58%), infection (42%), and infusion-related reaction (5%). Grade 3 or higher AEs included infection (21%), prolonged grade 3 or higher cytopenia (16%), neurotoxicity (11%), and CRS (5%).
TRAVERSE Trial Details
The TRAVERSE trial is a first-in-human, dose-escalation, multicenter trial evaluating ALLO-316, a novel off-the-shelf, HLA-unmatched, CD70-targeting CAR T-cell treatment. The trial is assessing ALLO-316 at four cell dose levels: 40M cells, 80M cells, 120M cells, and 240M cells. All patients enrolled had advanced or metastatic clear cell RCC with at least one measurable lesion and an ECOG Performance Score of 0 or 1. Prior treatment with an immune checkpoint inhibitor and VEGF-targeted therapy was a requirement for inclusion.
The primary endpoint of the study is the rate of dose-limiting toxicities, assessed at 28 days following infusion with ALLO-316.
Expert Commentary
"The RMAT designation for ALLO-316 highlights the transformative potential of our AlloCAR T platform to offer new hope for heavily pretreated patients with renal cell carcinoma who have exhausted standard treatment options," said Zachary Roberts, MD, PhD, Executive Vice President of Research & Development and Chief Medical Officer at Allogene Therapeutics. "This important milestone moves us closer to fulfilling the promise of 'off-the-shelf' CAR T therapy—delivering faster, more reliable, and widely accessible treatments. We remain optimistic about the future of ALLO-316 and its potential to be an important advancement for patients."
Samer A. Srour, MD, from The University of Texas MD Anderson Cancer Center, commented on the results, stating, "I am encouraged by these data highlighting the potential of an allogeneic CAR T as a new and much needed treatment modality for patients with renal cell carcinoma. Initial data from the TRAVERSE trial provides a proof-of-concept for the successful application of this novel CAR T product in the treatment of advanced renal cell carcinoma."
Allogene Therapeutics plans to present updated data from the TRAVERSE trial at the upcoming Society for Immunotherapy of Cancer Annual Meeting.
