310.3: Posoleucel as Preemptive Therapy for BKV Infection in Kidney Transplant Recipients: Safety, Tolerability and Efficacy in a Phase 2 Trial

Purpose: Kidney transplant (KT) recipients with BK viremia are at risk for BK virus (BKV) nephropathy and graft loss. There are no approved therapies for BKV infection. Posoleucel (PSL) is an off-the-shelf, allogeneic multivirus-specific T cell therapy that targets BKV as well as adenovirus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and JC virus. In a phase 2 trial of PSL in hematopoietic cell transplant recipients, 100% (27/27) of those with BKV disease had a clinical response. Methods: We are conducting a phase 2 double-blind placebo (PBO)-controlled study of PSL in 60 KT recipients with BK viremia (NCT04605484) in which patients are randomized 1:1:1 to receive PSL (Groups 1 and 2) or placebo for 12 weeks. PSL (4 × 107 PSL cells) is infused once a week for 3 weeks, then every 14 days (Group 1) or every 28 days (Group 2). After these 12-week dosing periods, patients are followed for 12 more weeks (observation period). The primary objective is safety and tolerability with a key secondary objective to assess changes in BK viremia. Results: This interim analysis of the ongoing study includes the first 37 patients enrolled as of 22 Feb 2022; 29 (78%) patients were male and 8 (22%) were female; 20 (54%) Caucasian, 10 (27%) African American, 4 (11%) Asian, and 3 (8%) were other race or not reported; 3 (8%) patients were of Hispanic ethnicity. Patients’ median age was 58.5 years, with a range from 32 to 75 years. Median day of PSL or PBO initiation post KT was 472 days (range 59 to 5158 days). Mean eGFR at start of the dosing period was 48 mL/min/1.73m2 (SD ∓18), and median plasma BK viral load was 5060 copies/mL (range 242 to 5,421,939 copies/mL). At a median follow-up of 40.5 days (range 1 to 173 days), PSL was well tolerated with no treatment-related serious adverse events, and 12 mild (grade 1), transient treatment-related adverse events in 4 patients. There were no discontinuations due to adverse events or adverse events of special interest, specifically no episodes of graft versus host disease, cytokine release syndrome, infusion reactions, or rejection. No patients developed de novo donor-specific antibodies. Kidney allograft function as measured by eGFR and creatinine remained stable during the study, with no change from baseline to latest assessment in either measurement. Mean (95% CI) changes in eGFR and creatinine were 0.9 mL/min/1.73 m2 (-2.9, 4.7) and 0.0 mg/dL (-0.2, 0.1), respectively. Updated safety and viral load data from all enrolled patients will be presented, including analyses of the effect of PSL versus PBO on other immune and viral endpoints. Conclusions: In this ongoing trial—the first randomized, double-blind placebo-controlled therapeutic trial of virus-specific T cell therapy in KT recipients with BK viremia—PSL was generally safe and well tolerated, supporting its continued evaluation as a preemptive therapy in KT recipients at risk for BKV nephropathy. This study was funded by AlloVir.