Treatment with the allogeneic chimeric antigen receptor (CAR) T-cell therapy ALLO-316 resulted in encouraging response rates and disease control rates for patients with metastatic clear cell renal cell carcinoma who did not respond to prior therapy, according to new findings presented by Srour et al at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract CT011).
Background
“We already know that CAR T-cell therapy is effective in patients with hematologic [malignancies], with several [U.S. Food and Drug Administration]–approved indications. Hence, we are adapting this same strategy for patients with solid tumors,” explained lead study author Samer Srour, MB ChB, MS, Assistant Professor of Stem Cell Transplantation & Cellular Therapy in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “In this trial, we [used] an allogeneic “off-the-shelf” CAR T-cell product [that offered] an additional benefit to our patients because we [were] able to get this novel treatment to our patients much faster,” he added.
ALLO-316 was genetically designed to target the CD70 protein, which is expressed in a variety of solid tumors and highly expressed in metastatic clear cell renal cell carcinoma. To reduce the risk of graft-vs-host disease, ALLO-316 cells also disrupted the CAR T-cell receptor alpha. Furthermore, the CD52 gene was knocked out to allow the use of ALLO-647, an anti-CD52 monoclonal antibody that works by depleting host T cells and improving the persistence of allogeneic CAR T cells.
Study Methods and Results
In the new multicenter, single-arm phase I TRAVERSE trial, the researchers evaluated the safety and preliminary efficacy of ALLO-316 in 18 patients with a median age of 63 years who had metastatic clear cell renal cell carcinoma and did not respond to prior therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors—17 of whom received an ALLO-316 infusion. The researchers reported that 82% of the study participants were male.
The patients received ALLO-316 at escalating doses of 40 million to 120 million CAR T cells; however, the study allowed doses of up to 240 million CAR T cells. Further, the patients involved in the trial received an ALLO-316 infusion 48 hours after lymphodepletion conditioning with fludarabine/cyclophosphamide—with or without ALLO-647.
Among 17 patients, the objective response rate was 18% and the disease control rate was 82%. For the nine patients who had confirmed CD70-positive disease, the objective response rate was 33% and the disease control rate was 100%.
Overall, the treatment had a manageable safety profile. About 65% (n = 11/17) of the patients experienced cytokine release syndrome, and the researchers observed no cases of graft-vs-host disease or immune effector cell–associated neurotoxicity syndrome. The maximum tolerated dose had not yet been reached at the time of the presentation.
Conclusions
“As we continue to determine the appropriate dose of ALLO-316 for patients, our results demonstrate not only a manageable safety profile but also very encouraging antitumor activity,” Dr. Srour highlighted. “We look forward to our [further] evaluation of data [in our ongoing effort to] learn about this novel CAR T-cell therapy approach in this patient population,” he concluded.
The researchers plan to continue optimizing the conditioning and determining the appropriate dose levels in a phase II trial, and hope to enroll further patients with CD70-positive tumors.
Disclosure: The research in this study was funded by Allogene Therapeutics as part of a strategic collaboration with The University of Texas MD Anderson Cancer Center. For full disclosures of the study authors, visit abstractsonline.com.
