ALLO-316 CAR T-Cell Therapy Shows Promise in Advanced Kidney Cancer
核心洞察
Updated results from the TRAVERSE study show that ALLO-316, a CD70 (搜索)-targeted CAR T-cell therapy, demonstrates durable activity in patients with treatment-refractory advanced kidney cancer (搜索).
A quarter of patients with high CD70 (搜索) expression (TPS ≥50) achieved objective responses, increasing to 40% with fludarabine/cyclophosphamide lymphodepletion, following a single infusion of ALLO-316.
The therapy exhibited a manageable safety profile, particularly after implementing a new strategy to minimize immune effector cell hemophagocytic lymphohistiocytosis-like syndrome.
LOUISVILLE, Ky. -- Updated findings from the TRAVERSE study indicate that ALLO-316, a CD70 (搜索)-targeted CAR T-cell therapy, continues to exhibit durable activity in patients with advanced kidney cancer (搜索) who have exhausted other treatment options. The results, presented at the International Kidney Cancer Symposium, offer a promising avenue for patients with relapsed/refractory clear cell renal cell carcinoma (搜索) (ccRCC).
Efficacy and Response Rates
The study revealed that 25% of patients with a CD70 (搜索) total positive score (TPS) of 50 or higher experienced objective responses to ALLO-316. This response rate increased to 40% in patients who underwent fludarabine/cyclophosphamide (FC) lymphodepletion. Notably, three out of six patients treated with a higher dose of the engineered therapy also responded positively.
"We're starting to see ongoing and deepening responses, particularly in patients with high CD70 (搜索) expression, after a single infusion of ALLO-316," said Dr. Ritesh R. Kotecha of Memorial Sloan Kettering Cancer Center (MSKCC). He also noted a decrease in alloreactive host CD70-positive T cells following ALLO-316 infusion, suggesting a targeted mechanism of action.
Safety Profile
A single infusion of ALLO-316 was associated with a manageable safety profile, especially after implementing a new strategy to mitigate immune effector cell hemophagocytic lymphohistiocytosis-like syndrome. Common side effects included cytokine release syndrome (CRS) in almost two-thirds of patients, fatigue, neutropenia, anemia, and nausea. Grade ≥3 adverse events included neutropenia (51%), anemia (33%), and thrombocytopenia (26%).
Study Design and Patient Population
The phase Ia-b TRAVERSE study included 39 patients (median age 60; 90% male; median time since original diagnosis 43 months), with 34 undergoing lymphodepletion and receiving a single infusion of the CAR T-cell product. The study consisted of dose-escalation and dose-expansion phases, with Phase Ib designed to establish a Phase II recommended dose and determine an appropriate CD70 (搜索) TPS cutoff for potential pivotal studies.
CD70 as a Target
The selection of CD70 (搜索) as a target stems from its high expression in approximately 80% of ccRCCs, with limited expression in normal tissues. ALLO-316, an off-the-shelf product derived from HLA-unmatched healthy donors, is designed to eliminate CD70+ tumor cells and CT70+ host T cells that can promote allo-rejection.
Future Directions
"The phase I TRAVERSE trial supports further evaluation of ALLO-316 in CD70 (搜索)-positive RCC and other CD70-positive malignancies. Enrollment is ongoing at the phase Ib regimen," Kotecha stated. The ongoing research aims to refine dosing strategies and identify optimal patient populations for this promising therapy.
Expert Commentary
Dr. Nizar Tannir of MD Anderson Cancer Center emphasized the importance of continuing this research path for patients with limited options, acknowledging the toxicities but highlighting the progress made in other hematologic malignancies with similar approaches. Dr. Sumanta Pal of City of Hope (搜索) stressed the need for a robust rheumatology team to manage potential toxicities associated with CAR T-cell therapy.