ALLO-316 has shown activity in patients with heavily pretreated, advanced clear cell renal cell carcinoma (RCC), according to study results presented at the AACR Annual Meeting 2023.
ALLO-316 is a chimeric antigen receptor (CAR) T-cell therapy targeting CD70, explained study presenter Samer Srour, MBChB, of the University of Texas MD Anderson Cancer Center in Houston.
ALLO-316 has the TCRα constant gene knocked out to reduce the risk of graft-vs-host disease and the CD52 gene knocked out to permit the use of ALLO-647, an anti-CD52 antibody, to deplete host T cells without affecting the CAR-T cells. The CAR is also designed to avoid fratricide, and it includes a CD20 mimotope-based intra-CAR off switch that allows the CAR-T cells to be eliminated with rituximab.
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The researchers evaluated ALLO-316 in the phase 1 TRAVERSE study (ClinicalTrials.gov Identifier: NCT04696731), which enrolled 19 patients with advanced clear cell RCC. The patients’ median age was 62 (range, 50-70) years, 84% were men, 100% had stage IV disease, and 79% had undergone nephrectomy. Patients had received a median of 3 prior lines of therapy (range, 1-8).
After enrollment, patients underwent lymphodepletion with fludarabine and cyclophosphamide for 3 days, with or without ALLO-647. This was followed by ALLO-316 at varying dose levels. Patients started conditioning a median of 5 days after enrollment, and they received ALLO-316 at doses of 40 x 106 (n=9), 80 x 106 (n=8), or 120 x 106 (n=2).
The median follow-up was 7.8 months, and 18 patients were evaluable for efficacy. The overall response rate (ORR) was 17%, and the disease control rate (DCR) was 89%.
Among the 10 patients with CD70-positive disease, the ORR was 30%, and the DCR was 100%. The median progression-free survival in this group was 5.0 months.
Nineteen patients were evaluable for safety. Sixty-eight percent of patients experienced neurotoxicity, 58% developed cytokine release syndrome (CRS), and 42% had infections.
Grade 3 or higher adverse events included 4 infections, 3 cases of prolonged cytopenia, 2 cases of neurotoxicity, and 1 case of CRS. One patient developed COVID-19 and died of respiratory failure. This was deemed unrelated to treatment.
“The safety profile overall was consistent with what we see with autologous CAR T-cell products,” Dr Srour said. “We are very encouraged by the antitumor activity with these low dose levels. We are hoping to finish accrual by the end of 2023 and go to the expansion phase and also to include additional tumor subtypes.”
Disclosures: This research was supported by Allogene Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Srour S, Kotecha R, Curti B, et al. A phase 1 multicenter study (TRAVERSE) evaluating the safety and efficacy of ALLO-316 following conditioning regimen in pts with advanced or metastatic clear cell renal cell carcinoma (ccRCC). AACR 2023. April 14-19, 2023. Abstract CT011.
