Allogene announces Phase 1 data on ALLO-316 in advanced RCC

Allogene Therapeutics (ALLO) will concurrently present new data from the Phase 1 TRAVERSE trial in an oral presentation at the 2024 International Kidney Cancer Symposium and a poster session at The Society for Immunotherapy of Cancer’s Annual Meeting. The trial evaluates ALLO-316, the Company’s first AlloCAR T product candidate for the potential treatment of solid tumors. The ongoing Phase 1 TRAVERSE trial is enrolling patients with advanced or metastatic renal cell carcinoma who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy. These presentations highlight compelling evidence of CAR T activity and anti-tumor efficacy in 26 patients with RCC tumors known to be CD70 positive who were evaluable for efficacy outcomes. As of the October 14, 2024 data cutoff, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was five days. Data from dose escalation cohorts and ongoing Phase 1b expansion cohort are included in the presentations. The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 following a standard FC500 lymphodepletion regimen. The Phase 1b expansion cohort is expected to ultimately include approximately 20 patients. Additional data from the Phase 1b expansion cohort is expected to be announced in mid-2025. Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score of greater than or equal to50% who received DL2. Patients with a TPS of greater than or equal to50% comprise the majority of patients with advanced or metastatic RCC. Of those with a TPS greater than or equal to50, 76% experienced a reduction in tumor burden. Two of six patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at greater than or equal to4 months. The most common all-grade adverse events were cytokine release syndrome, fatigue, neutropenia, decreased white blood cell count, anemia and nausea. Immune effector cell-associated neurotoxicity syndrome was minimal at 8% and no graft-versus-host disease occurred. TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first. IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH. Two patients developed an inflammatory syndrome prior to the existence of IEC-HS as a term in MedDRA, which has been updated as of September 2023. Two DLT events of autoimmune hepatitis and cardiogenic shock were reported. Each event occurred in 2 separate participants who received FCA lymphodepletion and DL2 of ALLO-316. Three Grade 5 treatment-related adverse events were reported: 1) cardiogenic shock, which was one of the 2 DLT events; 2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316. This participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation; 3) failure to thrive in a participant 16 months after treatment with ALLO-316. This subject had tumor response of stable disease at month 12 and no interval scans to evaluate disease status prior to death.