P1446: PHASE I STUDY DATA UPDATE OF PHE885, A FULLY HUMAN BCMA-DIRECTED CAR-T CELL THERAPY MANUFACTURED USING THE T-CHARGETM PLATFORM FOR PATIENTS WITH RELAPSED/REFRACTORY (R/R) MULTIPLE MYELOMA (MM)

Abstract

Background: Chimeric antigen receptor (CAR)-T cell therapy (tx) is approved for treatment of r/r MM. However, prolonged product manufacturing times and a need for longer duration of response are a major obstacle in this population, necessitating fast manufacture of a reliable and durable CAR-T cell product. Aims: Herein we report updated clinical data from a Phase I trial assessing the fully human B-cell maturation antigen (BCMA) CAR-T cell product PHE885 in adult patients (pts) with r/r MM. Methods: This multicenter, open-label study (NCT04318327) characterizes the safety and efficacy of PHE885 manufactured using the novel T-ChargeTM platform, which takes <2 d to manufacture the final product and relies on in vivo expansion after CAR-T cell infusion. Pts with MM r/r to ≥2 prior lines of tx, including an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody, were eligible. Pts received fludarabine and cyclophosphamide for lymphodepletion prior to a single PHE885 intravenous injection. Primary objectives were safety, including dose-limiting toxicities (DLTs) and adverse events (AEs). Secondary objectives included clinical response, T-ChargeTM process evaluation, and cellular kinetics. Results: At abstract submission, 22 pts were infused with PHE885 at the following fixed doses: 2.5×106 (n=4), 5×106 (n=12), 10×106 (n=5), and 14.3×106 (n=1) CAR-T cells; 15 pts (4 at 2.5×106, 10 at 5×106, and 1 at 14.3×106) were evaluable for safety and efficacy at the data cutoff for the abstract (October 13, 2021). Longer follow up of these 15 pts and data from additional pts treated at doses of 5×106 and 10×106 will be presented at the annual meeting. Of the 15 pts evaluable at data cutoff, DLTs were reported in 3 pts and included asymptomatic grade (gr) 3 transaminitis (n=1, 14.3×106), asymptomatic gr ≥3 elevated pancreatic enzymes (n=1, 5×106), and gr 4 neutropenia (n=1, 2.5×106). Most frequent tx-related gr ≥3 AEs included neutropenia (n=15, 100%), anemia (n=13, 87%), and thrombocytopenia (n=11, 73%). All pts experienced cytokine release syndrome (CRS) per Lee 2014 criteria; 2 had gr ≥3 CRS (n=1, 5×106; n=1, 14.3×106). Median times to CRS onset and resolution were 7 d (range, 4-12 d) and 11 d (range, 9-22 d), respectively. Tocilizumab (n=13, 87%), steroids (n=11, 73%), anakinra (n=4, 27%), and pressors (n=3, 20%) were used to manage CRS. Gr 2 neurotoxicity occurred in 4 pts (27%). Pts had an overall response rate of 93%, stringent complete response in 33%, very good partial response (VGPR) in 20%, and PR in 40%. Of evaluable pts at 3 mo post infusion, 43% (3/7) had minimal residual disease (MRD) at <10–5 sensitivity[JC(1], while 33% (2/6) were MRD negative at <10–6 by next-generation sequencing. Robust expansion of BCMA CAR-T cells was observed in all pts via qPCR and flow cytometry; maximum expansion (geometric mean Cmax) was 316,000 copies/μg by qPCR and 76% of circulating T cells by flow cytometry. Maximum expansion was reached at a median of 14.2 d by qPCR (13.9 d by flow cytometry). Naive-like T cells present in the leukapheresis were preserved during manufacturing of most PHE885 products as measured by flow cytometry, and an increase in naive/Tscm populations is observed in ≥VGPR pts post-infusion. Summary/Conclusion: Low doses of PHE885 manufactured by T-ChargeTM in <2 d have a manageable safety profile and encouraging clinical activity in pts with r/r MM. PHE885 expands rapidly in vivo, persists for prolonged periods, and demonstrates a relatively naive T-cell phenotype.