A phase 1 TRAVERSE trial (NCT04696731) evaluating ALLO-316, an off-the-shelf CAR T-cell therapy, has demonstrated a 50% overall response rate (ORR) and a 33% confirmed response rate in patients with CD70-positive renal cell carcinoma (RCC) whose tumors had a proportion score (TPS) of 50% or greater. These findings, presented at the 2024 International Kidney Cancer Symposium (IKCS) and the Society for Immunotherapy of Cancer's (SITC) annual meetings, suggest a potential new treatment avenue for patients with advanced RCC who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy.
Efficacy and Patient Outcomes
As of the data cutoff on October 14, 2024, the trial had enrolled 39 patients, with 26 having confirmed CD70-positive RCC and being evaluable for efficacy. Notably, 76% (16/21) of patients with a TPS ≥50% experienced a reduction in tumor burden. Furthermore, 33% (2/6) of patients with high TPS who received the phase 1b expansion regimen exhibited durable responses lasting four months or more.
Samer A. Srour, MD, assistant professor at The University of Texas MD Anderson Cancer Center, commented on the results, stating, "We are encouraged with results like ALLO-316 and some others. We are getting into that new era where we will, hopefully soon in the coming few years, be able to establish some sort of new standards."
Mechanism and Advancement
ALLO-316 leverages CD70 CAR-intrinsic Dagger® technology to drive cell expansion and persistence, potentially marking a significant advancement in allogeneic cell therapies. Zachary Roberts, MD, PhD, executive vice president of research and development and chief medical officer of Allogene Therapeutics, highlighted the therapy's potential, noting that the data demonstrates significant antitumor activity in patients with metastatic disease resistant to multiple therapeutic classes, even with standard lymphodepletion.
Safety Profile
The trial also provided insights into the safety profile of ALLO-316. The most common all-grade adverse events included cytokine release syndrome (with only one case being grade 3 or higher), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%), and nausea (51%). Immune effector cell-associated neurotoxicity syndrome was observed in 8% of patients. Importantly, no graft-vs-host disease occurred.
Two dose-limiting toxicity (DLT) events were reported: autoimmune hepatitis and cardiogenic shock, each occurring in separate patients who received FC300 plus ALLO-647 lymphodepletion and dose level 2 of ALLO-316.
Specific Adverse Events
Further details on treatment-related adverse events included cardiogenic shock (one of the DLTs), sepsis due to multidrug-resistant Klebsiella pneumoniae in a patient with a prior history of muscle abscess and bacteremia from the same pathogen, and failure to thrive 16 months post-treatment in a patient with stable disease at 12 months.
