FDA grants Regenerative Medicine Advanced Therapy designation to ALLO-316 for RCC

The FDA has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-316, an investigational AlloCAR T product for adult patients with CD70-positive advanced or metastatic renal cell carcinoma (RCC) who have received prior immune checkpoint inhibitor and VEGF-targeting therapy, Allogene Therapeutics announced in a news release.¹

ALLO-316 was previously granted a fast track designation in March 2022.

An RMAT designation is granted to products that are designed to treat, modify, reverse, or cure serious or life-threatening diseases and have preliminary clinical data suggesting that it can address an unmet medical need. Under the designation, ALLO-316 can benefit from more frequent interaction with the FDA to potentially accelerate the development and review of the therapy.

ALLO-316 was previously granted a fast track designation by the FDA for the same indication in March 2022.²

“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, in the news release.¹ “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.”

The RMAT designation is supported by interim data from the ongoing phase 1 TRAVERSE trial (NCT04696731), which were initially reported at the American Association of Cancer Research (AACR) Annual Meeting in April 2023.³

In total, 19 patients with clear cell RCC were enrolled in the study at the time of data cutoff, of whom 18 were included in the efficacy analysis. Among these patients, the disease control rate was 89%, and the overall response rate was 17%.

Further, 10 patients had CD70-expressing RCC. Among these patients, the disease control rate was 100%, and the overall response rate was 30%. The longest response lasted 8 months. In this subset, the median progression-free survival was 5.0 months. Data also showed that a higher baseline tumor CD70 immunohistochemistry H-Score was found to correlate with greater tumor reduction.

The safety profile for ALLO-316 was generally consistent with that of otherautologous CAR T therapies. Adverse events (AEs) of any grade included neurotoxicity (68%),cytokine release syndrome (CRS; 58%), infection (42%), and infusion-related reaction (5%). AEs of grade 3 or higher included infection (21%), prolonged grade 3 or higher cytopenia (16%), neurotoxicity (11%), and CRS (5%).

“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,” said Samer A. Srour, MD, The University of Texas MD Anderson Cancer Center, Houston, in a news release on the results.⁴ “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.”

TRAVERSE is a first-in-human, dose-escalation, multicenter trial of ALLO-316, which is a novel off-the-shelf, HLA-unmatched, CD70-targeting CAR T-cell treatment. The trial is assessing ALLO-316 at 4 cell dose levels: DL1=40M cells, DL2= 80M cells, DL3=120M cells, and DL4= 240M cells.

All patients included in the trial had advanced or metastatic clear cell RCC with at least 1 measurable lesion and an ECOG Performance Score of 0 or 1. Prior treatment with an immune checkpoint inhibitor and VEGF-targeted therapy was required. The median time from enrollment in the trial to the start of therapy was 5 days.

The primary end point for the study is the rate of dose-limiting toxicities, as assessed at 28 days following infusion with ALLO-316.

The company plans to present updated data from the TRAVERSE trial at the upcoming Society for Immunotherapy of Cancer Annual Meeting.

References

1. 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. Published online and accessed October 29, 2024. https://www.globenewswire.com/en/news-release/2024/10/29/2970809/0/en/Allogene-Therapeutics-Receives-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-ALLO-316-an-AlloCAR-T-Investigational-Product-for-Adult-Patients-with-Advanced-or-Met.html

2. Allogene Therapeutics receives FDA Fast Track Designation for its first solid tumor candidate, ALLO-316 in the treatment of renal cell carcinoma. News release. Allogene Therapeutics. March 10, 2022. Accessed October 29, 2024. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-receives-fda-fast-track-designation-its

3. Srour SA, Kotecha R, Curti B, et al. A phase 1 multicenter study (TRAVERSE) evaluating the safety and efficacy of ALLO-316 following conditioning regimen in pts with advanced or metastatic clear cell renal cell carcinoma (ccRCC). Presented at: 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, FL. Abstract CT011

4. Allogene Therapeutics presents interim phase 1 data on ALLO-316 in renal cell carcinoma at the American Association of Cancer Research (AACR) Annual Meeting. News release. Allogene Therapeutics. April 17, 2023. Accessed October 29, 2024. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-presents-interim-phase-1-data-allo-316