Allogeneic CAR T-Cell Therapy ALLO-316 Demonstrates Durable Responses in Advanced Clear Cell Renal Cell Carcinoma
核心洞察
The Phase I TRAVERSE trial of ALLO-316, an off-the-shelf CD70 (搜索)-targeted CAR T-cell therapy, achieved a 31.3% objective response rate in heavily pretreated advanced ccRCC patients with high CD70 expression.
Half of patients in the Phase 1b cohort experienced disease control, with some responses lasting over a year after a single infusion and one patient later achieving a complete response.
The study provides the first clinical proof-of-concept that allogeneic CAR T-cell therapy can be active in solid tumors, with a manageable safety profile and no severe neurotoxicity or graft-versus-host disease observed.
Patients with advanced clear cell renal cell carcinoma (搜索) (ccRCC) who were treated with the CD70 (搜索)-targeted allogeneic chimeric antigen receptor (CAR) T-cell therapy ALLO-316 experienced encouraging results with durable responses, according to results of the Phase 1a/b TRAVERSE clinical trial led by researchers at The University of Texas MD Anderson Cancer Center. The findings, published in the Journal of Clinical Oncology, represent the first clinical proof-of-concept that an off-the-shelf CAR T-cell therapy can demonstrate meaningful activity in a solid tumor.
"Patients with advanced clear cell renal cell carcinoma (搜索) who progress on standard therapies have very limited treatment options and historically poor outcomes," said principal investigator Samer Srour, M.B Ch.B., associate professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. "For years, CAR T cell therapies have transformed outcomes in blood cancers, but reproducing that success in solid tumors has proven to be challenging. These results represent an important milestone in expanding the promise of CAR T cell therapy into kidney cancer and other solid tumors."
Trial Design and Patient Population
The TRAVERSE trial enrolled 51 patients with stage 4 disease who had previously received a median of four prior lines of therapy. Of these, 46 patients received treatment and had a median follow-up time of 28.8 months. The Phase 1a portion of the study established the recommended dose and lymphodepletion regimen for ALLO-316 while demonstrating a manageable safety profile.
In the Phase 1b expansion cohort, 23 heavily pretreated patients with positive CD70 (搜索) expression were enrolled, 20 of whom received ALLO-316. All patients had progressed after treatment with immune checkpoint inhibitors and tyrosine kinase inhibitors, reflecting a population with severely limited remaining options.
Efficacy Results
The therapy achieved an objective response rate (ORR) of 25.0% in the recommended Phase 1b regimen. Notably, in patients with high CD70 (搜索) expression—defined as a tumor proportion score (TPS) of 50% or greater—the ORR rose to 31.3%. Half of the patients in the Phase 1b cohort experienced disease control, with some patients remaining in continued response for over a year after a single infusion of ALLO-316.
Median overall survival for the Phase 1b cohort was 15.2 months, while median overall survival was not reached in patients with high CD70 (搜索) expression. These findings suggest that CD70 expression levels may serve as a predictive biomarker to identify patients most likely to benefit from treatment with ALLO-316.
Jad Chahoud, Chief Scientific and Innovation Officer at Orlando Health Cancer Institute and a co-author on the study, highlighted a particularly compelling outcome: "Even more rewarding personally, after the data cutoff, one of my patients who was in a partial response has now achieved a complete response and remains off all therapy. Moments like these remind us why we continue to push the boundaries of cancer research for our patients."
Safety Profile
Overall, the treatment had a manageable safety profile consistent with the known experience of CAR T-cell therapies in blood cancers. No severe neurotoxicity or graft-versus-host disease was observed, a critical consideration for allogeneic cell therapies.
What Is ALLO-316?
ALLO-316 is an off-the-shelf CAR T-cell therapy designed to target CD70 (搜索), a protein commonly expressed on kidney cancer cells. Unlike traditional autologous CAR T-cell therapies manufactured from a patient's own cells, ALLO-316 is derived from healthy donor cells and engineered to overcome immune rejection while attacking cancer cells. This allogeneic approach offers potential advantages in manufacturing scalability, reduced vein-to-vein time, and broader patient accessibility.
Addressing an Unmet Need
ccRCC is the most common form of kidney cancer and typically causes no symptoms until diagnosed in late stages. While immune checkpoint inhibitors and targeted therapies have improved outcomes, many patients eventually stop responding to available treatments. Most patients in the TRAVERSE trial had exhausted multiple available therapies and faced a poor prognosis, with survival often measured in months.
Researchers say the TRAVERSE trial provides evidence that allogeneic CAR T-cell therapies can be successfully deployed against solid tumors. Further research is ongoing to advance the clinical development of ALLO-316 in ccRCC and to expand this novel therapy into other CD70 (搜索)-expressing tumors. As Chahoud noted, "The journey of CAR T-cell therapy in solid tumors is just beginning."