FDA Grants Regenerative Medicine Advanced Therapy Designation to ALLO-316 in CD70+ Advanced RCC

FDA

The investigational allogeneic CAR T-cell therapy ALLO-316 has received regenerative medicine advanced therapy (RMAT) designation from the FDA for the treatment of adult patients with CD70-positive advanced or metastatic renal cell carcinoma (RCC).¹

RMAT designation was supported by data from the phase 1 TRAVERSE trial (NCT04696731), which were initially presented at the 2023 AACR Annual Meeting. Additional data will be presented at the 2024 SITC Annual Meeting in November.

Previously reported data demonstrated that all evaluable patients (n = 18) experienced an overall response rate (ORR) of 17% and a disease control rate (DCR) of 89%. In patients with CD70-positive disease (n = 10), the ORR and DCR were 30% and 100%, respectively. The CD70-positive subgroup included 2 patients who achieved a confirmed partial remission (PR) and a third patient who had an unconfirmed PR. The longest response persisted until month 8, and a trend toward increased tumor shrinkage was observed in patients with higher levels of CD70.²

In patients evaluable for safety (n = 19), data showed the adverse effect (AE) profile of ALLO-316 was consistent with the profiles of autologous CAR T-cell therapies. One dose-limiting toxicity (DLT) of grade 3 autoimmune hepatitis was reported at the second dose level of 80 x 10⁶ cells.

The most common AEs included cytokine release syndrome (CRS; any-grade, 58%; grade ≥3, 5%), infusion-related reaction (5%; 0%), neurotoxicity (68%; 11%), and infection (42%; 21%). Prolonged grade 3 or higher cytopenia occurred in 16% of patients. No instances of immune effector cell–associated neurotoxicity syndrome or graft-vs-host disease were reported. One patient experienced grade 5 COVID-19 that was deemed unrelated to study treatment.

“The RMAT designation for ALLO-316 highlights the transformative potential of our AlloCAR T™ platform to offer new hope for heavily pretreated patients with RCC who have exhausted standard treatment options,” Zachary Roberts, MD, PhD, executive vice president of Research & Development and chief medical officer at Allogene Therapeutics, stated in a news release.¹ “This important milestone moves us closer to fulfilling the promise of ‘off-the-shelf’ CAR [T-cell] 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 ongoing TRAVERSE trial is enrolling patients 18 to 75 years of age with histologically confirmed RCC featuring a predominant clear cell component who received prior treatment with an immune checkpoint inhibitor and a VEGF inhibitor in the advanced and/or metastatic setting.³ Key inclusion criteria consist of at least 1 measurable lesion per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; the absence of donor-specific anti-HLA antibodies; and adequate hematological, renal, liver, pulmonary, and cardiac function.

Patients are being excluded if they have central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression; however, those with CNS metastatic disease are allowed to participate if CNS disease is controlled and stable for at least 4 weeks. Other exclusion criteria consist of clinically significant CNS dysfunction; any other active malignancy within 3 years of enrollment; prior treatment with anti-CD70 therapy; a thyroid disorder other than hypothyroidism controlled on stable dose of hormone-replacement therapy; and prior treatment with anti-CD52 monoclonal antibody within 12 months of enrollment.

During dose escalation, patients underwent lymphodepletion followed by ALLO-316 given at 4 x 10⁶ cells, 8 x 10⁶ cells, 12 x 10⁶ cells, or 24 x 10⁶ cells.² Lymphodepletion consisted of fludarabine and cyclophosphamide with or without the CD52 monoclonal antibody ALLO-647.³

The incidence of DLTs for increasing doses of ALLO-316 and DLTs for ALLO-647 plus fludarabine and cyclophosphamide are the trial’s primary end points.

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. October 29, 2024. Accessed October 30, 2024. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-receives-fda-regenerative-medicine
2. Allogene Therapeutics presents interim phase 1 sata 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 30, 2024. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-presents-interim-phase-1-data-allo-316
3. Safety and efficacy of ALLO-316 in subjects with advanced or metastatic clear cell renal cell carcinoma (TRAVERSE). ClinicalTrials.gov. Updated October 31, 2023. Accessed October 30, 2024. https://clinicaltrials.gov/study/NCT04696731