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Dr Srour on the Mechanism of Action of ALLO-316 in Metastatic Clear Cell RCC

Samer A. Srour, MB ChB, MS, discusses the mechanism of action of ALLO-316, which is being investigated for the treatment of patients with advanced or metastatic clear cell renal cell carcinoma, and details safety findings from the phase 1 TRAVERSE study evaluating ALLO-316 in this patient population.

Samer A. Srour, MB ChB, MS, assistant professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the mechanism of action of ALLO-316, which is being investigated for the treatment of patients with advanced or metastatic clear cell renal cell carcinoma (RCC), and details safety findings from the phase 1 TRAVERSE study (NCT04696731) evaluating ALLO-316 in this patient population.

Preliminary data presented at the 2023 AACR Annual Meeting showed ALLO-316 demonstrated antitumor activity and a favorable safety profile. In the efficacy evaluable population (n = 18), the overall response rate (ORR) was 17%, and the disease control rate (DCR) was 89%. Among patients with CD70-positive RCC (n = 10), 3 patients (30%) achieved a partial response, the DCR was 100%, and the median progression-free survival was 5.0 months.

TRAVERSE is a first-in-human study of ALLO-316, which is an off-the-shelf, CD70-targeted CAR T-cell therapy. CD70 is a tumor antigen expressed in several solid tumors and hematologic malignancies, and it is highly expressed in patients with kidney cancer, Srour notes. ALLO-316 is being examined in patients with RCC who have failed the standard therapies, who generally have a poor prognosis, he adds.

Findings from the dose-escalation portion of the trial showed that no unexpected safety signals were reported. One patient treated at the second dose level with conditioning therapy and ALLO-647 experienced a dose-limiting toxicity of grade 3 type 2 autoimmune hepatitis. Additionally, 2 patients had grade 3 neurotoxicity (syncope and fatigue), and 1 patient died due to respiratory failure from COVID-19 infection, which was unrelated to the study treatment.

Cytokine release syndrome (CRS) was manageable, and no instances of immune effector cell–associated neurotoxicity syndrome or graft-vs-host disease were reported.

Many challenges have been faced with the investigation of CAR T-cell therapies in solid tumors, as many of the studies to date have not demonstrated a clinically meaningful benefit. However, ALLO-316 elicited responses in this study, Srour concludes.

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