Dr Srour on the Phase 1 TRAVERSE Study of ALLO-316 in Metastatic Clear Cell RCC

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 study design of the phase 1 TRAVERSE study (NCT04696731), and key data on the use of ALLO-316 in patients with advanced or metastatic clear cell renal cell carcinoma (RCC).

The first-in-human TRAVERSE study utilized a 3+3 dose-escalation design to identify the maximum tolerated dose of the anti-CD70 allogeneic CAR T-cell product ALLO-316 for adults with advanced or metastatic clear cell RCC, Srour begins. A total of 19 patients enrolled on the study received ALLO-316 at escalating dose levels of 40 x 10⁶ CAR+ cells (n = 9), 80 x 10⁶ CAR+ cells (n = 8), and 120 x 10⁶ CAR+ cells (n = 2). Prior to ALLO-316 infusion, patients received a daily lymphodepletion regimen consisting of 30 mg/m2 of fludarabine and 300 mg/m2 of cyclophosphamide with or without 10 mg of the anti-CD52 agent ALLO-647, Srour reports. The trial’s primary end point was a target incidence rate for dose-limiting toxicities (DLTs) in the first 28 days after ALLO-316 infusion.

Preliminary efficacy data from this study show that the agent demonstrated both antitumor activity and a favorable safety profile in a heavily pretreated patient population, Srour says. In the efficacy evaluable population (n = 18), the overall response rate (ORR) was 17%, and the disease control rate (DCR) was 89%. This result was more pronounced in the 10 patients with CD70-positive clear cell RCC, who achieved a DCR of 100% and an ORR of 30%, Srour notes.

In terms of safety, the agent’s toxicity profile is comparable to that of autologous CAR T-cell products in this patient population. The regimen elicited one dose-limiting toxicity which was grade 3 type 2 autoimmune hepatitis at the second dose level. There were no reports of immune effector cell–associated neurotoxicity syndrome or graft-vs-host disease. The incidence of cytokine release syndrome (CRS) was predominantly low grade, with 11 patients reporting any-grade CRS and 1 patient reporting a grade 3 or greater CRS event. 

Although these are early findings, they indicate that the regimen may provide a safe and effective option for heavily pretreated patients who historically have poorer prognosis, Srour emphasizes. Moreover, patients show promising responses to lower dose levels of ALLO-316, Srour concludes.

Disclosure: Dr Srour reports receiving honorarium for consulting/speaking for Novartis Pharmaceuticals.