Allogene Therapeutics Provides Updated Phase 1 Data Highlighting Durable Responses with ALLO-316 in Heavily Pretreated Advanced Renal Cell Carcinoma at ASCO

Allogene Therapeutics announced positive Phase 1 trial results for ALLO-316, an allogeneic CAR T-cell therapy, in advanced renal cell carcinoma (RCC). The trial demonstrated a 31% confirmed response rate in patients with high CD70 expression, with four of five responders maintaining ongoing responses, including one ongoing remission over 12 months; the treatment also exhibited a manageable safety profile. These findings suggest that ALLO-316, leveraging Allogene's Dagger technology, could provide a meaningful clinical benefit for RCC patients who have exhausted other treatment options and represent a promising advancement in solid tumor therapy.

Analysis

Allogene Therapeutics (Nasdaq: ALLO) has presented compelling updated Phase 1 data for its allogeneic CAR T therapy, ALLO-316, in patients with advanced or metastatic renal cell carcinoma (RCC), particularly those with high CD70 tumor proportion scores (TPS ≥ 50%). In this key patient subgroup, a single dose of ALLO-316 achieved a 31% confirmed Overall Response Rate (ORR), with 44% of these patients experiencing at least a 30% reduction in tumor burden. The durability of these responses is noteworthy, as four out of five confirmed responders remain in response, including one patient in ongoing remission for over 12 months, and the median duration of response has not yet been reached. These outcomes were observed in a heavily pre-treated population who had exhausted multiple prior therapies. The trial highlighted Allogene's proprietary Dagger® technology, designed to enable robust CAR T cell expansion and tumor infiltration with a standard lymphodepletion regimen, positioning ALLO-316 as a potentially pioneering allogeneic CAR T product for solid tumors. The safety profile of ALLO-316 was reported as manageable and consistent with lymphodepletion and CAR T therapy; the most frequent Grade ≥3 events were hematologic, and no treatment-related Grade 5 events occurred. Cytokine release syndrome (CRS) was observed in 68% of patients (all Grade 1 or 2), and immune effector cell-associated neurotoxicity syndrome (ICANS) in 18% (all Grade 1 or 2), with no instances of graft-versus-host disease. Newly implemented strategies effectively mitigated Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS). The U.S. FDA's granting of Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations, coupled with support from CIRM, further underscores the therapeutic potential of ALLO-316 in addressing a significant unmet medical need in RCC and validates Allogene's AlloCAR T™ platform.

Key Decisions for Investors

• Investors should recognize the reported 31% ORR and durable responses in the CD70 TPS ≥ 50% RCC cohort as a significant clinical advancement for Allogene, potentially de-risking ALLO-316 and offering validation for its Dagger® technology in solid tumors.
• It is advisable to closely monitor upcoming catalysts for ALLO-316, including further maturation of response durability, data from larger patient cohorts or subsequent trial phases, and the evolving competitive landscape for allogeneic cell therapies in oncology.
• Consider the implications of the RMAT and Fast Track designations, which may expedite the development and regulatory review of ALLO-316, while remaining aware of the inherent clinical, regulatory, and financial risks associated with clinical-stage biotechnology companies.