Allogene Therapeutics Reports Promising Phase 1 Results for ALLO-316 in Advanced Renal Cell Carcinoma

New findings from Allogene Therapeutics, a biotechnology company specializing in allogeneic CAR T cell therapies, shine a light on the potential of their leading product candidate, ALLO-316, in treating solid tumors. Detailed results from the Phase 1 TRAVERSE trial, presented at two major medical conferences, underscore the promise of this innovative treatment for patients with advanced or metastatic renal cell carcinoma (RCC).

The ongoing Phase 1 TRAVERSE trial focuses on patients with advanced RCC who have not responded to previous treatments involving immune checkpoint inhibitors and VEGF-targeting therapies. To date, the study has enrolled 39 participants, 26 of whom have CD70-positive tumors and were assessed for efficacy. Notably, a single infusion of ALLO-316 led to a best Overall Response Rate (ORR) of 50% and a Confirmed Response Rate of 33% in patients with a CD70 Tumor Proportion Score (TPS) of 50% or higher. These patients represent the majority of individuals with advanced or metastatic RCC, with a significant 76% showing a reduction in tumor size.

Dr. Zachary Roberts, Chief Medical Officer at Allogene, commented on these findings, highlighting the significant tumor infiltration and cell expansion facilitated by the CD70 CAR-intrinsic Dagger technology within ALLO-316. This technology appears to enhance the robustness and persistence of the CAR T cells, even following standard lymphodepletion. The evidence gathered from the trial suggests that ALLO-316 could signify a major leap forward in allogeneic cell therapy for solid tumors.

Safety assessments have also returned promising results. Common adverse events included cytokine release syndrome (CRS), fatigue, neutropenia, decreased white blood cell count, anemia, and nausea. Severe neurotoxicity, such as immune effector cell-associated neurotoxicity syndrome (ICANS), was minimal and no instances of graft-versus-host disease (GvHD) were observed. Notably, new diagnostic and management algorithms effectively mitigated IEC-HS without compromising the efficacy of the CAR T treatment.

Additionally, the U.S. Food and Drug Administration (FDA) recently granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-316 based on its potential to address unmet medical needs in patients with advanced RCC. This designation, combined with previous Fast Track Designation (FTD) and financial support from the California Institute for Regenerative Medicine (CIRM), including a $15 million award, underscores the regulatory and financial backing for this innovative therapy.

Phase 1b of the trial is also underway, examining the safety and efficacy of ALLO-316 at a dose level of 80 million CAR T cells following a standard lymphodepletion regimen. It is anticipated that about 20 patients will be included in this expansion cohort, with additional data expected to be released by mid-2025. Preliminary findings from this cohort have already shown durable responses in a portion of patients, further validating the therapeutic potential of ALLO-316.

Overall, these developments indicate a promising future for ALLO-316 in the treatment of RCC and potentially other cancers expressing CD70. The combination of strong efficacy data, a manageable safety profile, and significant regulatory milestones positions Allogene Therapeutics at the forefront of advancing allogeneic CAR T cell therapies for solid tumors. The upcoming results from the Phase 1b expansion cohort will be eagerly awaited as they could further solidify the role of ALLO-316 in cancer treatment and potentially lead to broader clinical applications.