The CD70-targeted allogeneic chimeric antigen receptor (CAR) T-cell therapy CTX130 may be effective in patients with advanced clear cell renal cell carcinoma, according to findings presented by Srour et al at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract CT002) and simultaneously published by Pal et al in Cancer Discovery.
Background
Patients with metastatic clear cell renal cell carcinoma who do not benefit from current standard therapies may have limited treatment options and poorer prognoses. CTX130 was designed to target CD70, which is present at high levels in clear cell renal cell carcinoma and is known to play a role in the suppressive immune tumor microenvironment as a result of T-cell exhaustion and regulatory T-cell expansion. The therapy uses T cells from healthy donors edited to disrupt the TRAC and B2M genes and reduce graft-vs-host disease and donor rejection.
Study Methods and Results
In the new multicenter phase I COBALT-RCC study, the researchers examined the safety and efficacy of the CTX130 CAR T-cell therapy in 16 patients with advanced clear cell renal cell carcinoma and a median age of 63 years. The patients were divided into four dose-level cohorts.
Among the patients, 81% experienced clinical benefit, including 75% with stable disease. Further, one patient experienced a durable complete response of over 3 years. The researchers also reported an acceptable safety profile for CTX130 with manageable side effects.
Conclusions
The researchers hope their new findings provide a proof of concept, meriting further exploration of CD70-targeted CAR T-cell therapy in patients with clear cell renal cell carcinoma and other CD70-positive cancer types.
“Our trial presents the first and the longest durable response we have seen with an allogeneic, off-the-shelf, CAR T-cell therapy in the treatment of refractory solid tumors,” emphasized lead study author Samer Srour, MB ChB, Assistant Professor of Stem Cell Transplantation & Cellular Therapy at The University of Texas MD Anderson Cancer Center. “These findings are exciting and encouraging as we continue to improve treatment options for patients with clear cell renal cell carcinoma and other high-risk solid tumors who otherwise have poor outcomes,” he concluded.
The researchers are currently enrolling patients in a phase I/II clinical trial (ClinicalTrials.gov identifier NCT05795595) to evaluate the novel CAR T-cell therapy CTX131.
Disclosure: The research in this study was sponsored by CRISPR Therapeutics. For full disclosures of the study authors, visit abstractsonline.com and aacrjournals.org.
