Allogene Therapeutics' ALLO-316, an allogeneic CD70-directed CAR-T therapy, has shown promising results in patients with advanced or metastatic renal cell carcinoma (RCC) in the phase 1 TRAVERSE clinical trial (NCT04696731). The data, presented at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting, revealed notable anti-tumor activity, but also included reports of three on-study patient deaths.
Efficacy Results
The efficacy analysis included 26 patients with confirmed CD70-positive RCC. Among the 8 patients treated at dose-level 2 (80 million CAR T-cells) following standard lymphodepletion (fludarabine and cyclophosphamide), the best overall response rate (ORR) was 38% (3/8). In patients with a high CD70 Tumor Proportion Score (TPS ≥ 50%), the best ORR was 50% (3/6). The confirmed ORR, requiring subsequent confirmation of complete or partial response, was 25% (2/8) for the group of 8 patients and 33% (2/6) for those with high CD70 TPS. Across all 26 evaluable patients, the best ORR was 27% (7/26), with a confirmed ORR of 19% (5/26). Notably, 76% of patients with high CD70 TPS showed a decrease in tumor burden, and 33% of those treated with the phase 1b expansion regimen achieved durable responses lasting at least 4 months.
Zachary Roberts, MD, PhD, EVP, research and development and chief medical officer of Allogene, stated that ALLO-316 continues to show remarkable potency in the TRAVERSE trial. He added that the data demonstrates significant antitumor activity in patients with metastatic disease resistant to multiple therapeutic classes, potentially marking a major advancement in the field.
Safety Profile and Adverse Events
The safety analysis included 39 patients treated with ALLO-316. Common adverse events (AEs) included cytokine release syndrome (CRS) (62%), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%), and nausea (51%). Only one patient (3%) experienced grade 3 or higher CRS, and 8% experienced immune effector cell-associated neurotoxicity syndrome. No graft versus host disease was reported. Infections occurred in 62% of patients, with 31% experiencing grade 3 or higher infections. Neurotoxicity occurred in 44% of patients, with 31% experiencing grade 3 or higher neurotoxicity AEs. Immune effector cell (IEC) associated HLH-like syndrome (IEC-HS) occurred in 13% of patients, with 3% experiencing a grade 3 or higher case.
On-Study Deaths
Three patients died during the trial. One death was attributed to cardiogenic shock, considered a dose-limiting toxicity. Another patient died of sepsis from multidrug-resistant Klebsiella pneumoniae, having previously experienced related infections and receiving treatment for hyperinflammation. The third patient's death, occurring 16 months post-treatment, was attributed to "failure to thrive," with stable disease observed at 12 months but no subsequent scans to assess disease status.
Competitive Landscape
ALLO-316 is not the only CAR-T therapy in development for RCC. Invectys initiated a phase 1/2a clinical trial (NCT05672459) for its CAR-T therapy IVS-3001, targeting HLA-G-positive clear cell RCC and other HLA-G-positive solid tumors.
