Allogene Therapeutics' investigational allogeneic CAR T-cell therapy, ALLO-316, has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of adult patients with CD70-positive advanced or metastatic renal cell carcinoma (RCC). This designation aims to expedite the development and review of regenerative medicine therapies intended to treat serious conditions. The RMAT designation was supported by data from the phase 1 TRAVERSE trial (NCT04696731), with additional data to be presented at the 2024 SITC Annual Meeting in November.
Promising Phase 1 Data
Previously reported data from the TRAVERSE trial, initially presented at the 2023 AACR Annual Meeting, demonstrated encouraging antitumor activity. Among all evaluable patients (n = 18), the overall response rate (ORR) was 17%, and the disease control rate (DCR) was 89%. Notably, in patients with CD70-positive disease (n = 10), the ORR increased to 30%, and the DCR reached 100%. This subgroup included two patients who achieved a confirmed partial remission (PR) and a third patient with an unconfirmed PR. The longest response observed persisted until month 8, with a trend toward increased tumor shrinkage in patients with higher levels of CD70 expression.
Safety Profile
In terms of safety, data from 19 evaluable patients showed that the adverse effect (AE) profile of ALLO-316 was consistent with that 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, which was deemed unrelated to the study treatment.
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 RCC 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-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."
Trial Details
The ongoing TRAVERSE trial is enrolling patients aged 18 to 75 years with histologically confirmed RCC featuring a predominant clear cell component who have previously been treated with an immune checkpoint inhibitor and a VEGF inhibitor in the advanced and/or metastatic setting. Key inclusion criteria include at least one 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 excluded if they have central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression, although those with controlled and stable CNS metastatic disease for at least 4 weeks are allowed to participate. Other exclusion criteria include 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 a 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 at doses of 4 x 106 cells, 8 x 106 cells, 12 x 106 cells, or 24 x 106 cells. Lymphodepletion consisted of fludarabine and cyclophosphamide with or without the CD52 monoclonal antibody ALLO-647. The trial's primary endpoints are the incidence of DLTs for increasing doses of ALLO-316 and DLTs for ALLO-647 plus fludarabine and cyclophosphamide.
