2161. Posoleucel, an Allogeneic, Off-the-Shelf Multi-Virus Specific T Cell Therapy, for Severe, Drug-Refractory Viral Infections in Pediatric Patients Following HCT: Results from a Phase 2 Trial

Abstract Background Serious viral infections are a leading cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic cell transplant (allo-HCT). Most available antivirals have significant toxicities and suboptimal efficacy. Posoleucel (PSL) is an allogeneic, off-the-shelf multi-virus specific T cell investigational product to prevent or treat 6 viral infections (AdV, BKV, CMV, EBV, HHV-6, and JCV). In the phase 2 CHARMS trial of PSL in allo-HCT recipients with intractable viral infections, 95% of patients had a clinical response. Here we present the efficacy and safety data in pediatric patients (< 18 years) enrolled in CHARMS. Methods Allo-HCT patients who had failed antiviral therapy or were unable to tolerate antivirals to control BKV, CMV, AdV, EBV, HHV-6, and/or JCV infection received a single PSL infusion of 2×107 cells/m2. Patients with a response could receive up to 4 more doses after 4 weeks, at 2-week intervals. The primary endpoint of the study was safety and feasibility. Other endpoints included complete and partial clinical response, with complete response (CR) as return to normal range and resolution of signs/symptoms and partial response (PR) defined as ≥50% decrease in viral load and/or ≥50% improvement of clinical signs/symptoms assessed by 6 weeks post infusion. Results 18 pediatric patients received PSL (1 was treated for 2 infections separately). Of the 13 with 1 viral infection, 6 (46%) had BKV, 3 (23%) CMV, 2 (15%) AdV, 2 (15%) HHV-6, and none EBV or JCV. Five (38%) had >1 infection: 3 had 2 infections, 1 had 3 infections, and 1 had 1 viral infection at each of 2 enrollments. 56% of patients received one infusion. PSL was generally well tolerated. Besides fever in 7 patients, we observed no toxicities or symptoms of CRS. Five cases of acute graft-versus-host disease (aGVHD) were observed; 3 in patients with history of aGVHD (2 had aGVHD at baseline). Both de novo cases of GVHD were Grade 1. 100% of patients achieved a clinical response (CR or PR) by 6 weeks including all 5 patients infected with multiple target viruses. Four of 6 patients with AdV infection had CR. Conclusion PSL treatment was well tolerated. All pediatric patients receiving PSL had a clinical response. Phase 3 studies including pediatric patients are in progress. Disclosures Ifigeneia Tzannou, MD, AlloVir: Advisor/Consultant Carlos Ramos, MD, Novartis: Advisor/Consultant Swati Naik, MD, Bellicum: Travel, Accomodation, Expenses Iain Fraser, MD, DPhil, AlloVir: Employee|AlloVir: Stocks/Bonds Marshelle Warren, MD, AlloVir: Advisor/Consultant Badrish Patel, MD, AlloVir: Employee|AlloVir: Stocks/Bonds Dany Ward, RN, AlloVir: Employee|AlloVir: Stocks/Bonds Ann Leen, PhD, AlloVir: Advisor/Consultant|AlloVir: Stocks/Bonds Bilal Omer, MD, AlloVir: Grant/Research Support.