PB1983: TRIAL-IN-PROGRESS: PHASE II STUDY OF PHE885, A B-CELL MATURATION ANTIGEN-DIRECTED CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY, IN ADULTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA

Background: New therapies for multiple myeloma (MM) such as immunomodulatory drugs (IMiD), proteasome inhibitors (PI), and CD38-targeted monoclonal antibodies (anti-CD38 mAb) enhance the overall survival (OS) of patients (pts) with relapsed and/or refractory (r/r) MM. However, MM remains incurable, with insufficient rates and duration of response, and progression-free survival (PFS). B-cell maturation antigen (BCMA) is expressed in MM cells and is essential for maintenance of long-lived plasma cells. It is a clinically validated target in therapies that have been developed to address unmet needs in MM. T-Charge™ is a novel platform that retains the naive/Tscm immunophenotype of the input leukapheresis and reduces the manufacturing process time to <2 days. This simplified manufacturing process may reduce the need for bridging therapy, and the preserved T-cell stemness has the potential to provide high rates of durable responses. A preliminary Phase I study of PHE885, a fully human BCMA-directed CAR-T cell therapy manufactured using T-Charge™, in 15 pts showed a 93% overall response rate (ORR) across all dose levels and a manageable safety profile, suggesting robust efficacy. Aims: To determine efficacy and safety of PHE885 in adults with r/r MM who have failed ≥3 prior lines of therapy. Methods: This is a Phase II, open-label, single-arm, multicenter trial of PHE885 in pts with r/r MM (NCT05172596). The trial population includes adults aged ≥18 y with r/r MM who failed ≥3 different prior lines of therapy, including an IMiD, a PI, and an anti-CD38 mAb, and who have measurable disease at enrollment per International Myeloma Working Group (IMWG) criteria. Patients should not have received a prior anti-BCMA therapy. No MM-specific therapy is allowed prior to eligibility confirmation. After obtaining informed consent, eligible pts will undergo leukapheresis for PHE885 manufacture. Following receipt of the final product, lymphodepletion (LD) chemotherapy will commence 5 days before PHE885 infusion as a 3-day cycle unless the pt has significant cytopenia. Optional bridging therapy can be given to pts who have significant worsening of clinical status prior to PHE885 infusion. After LD chemotherapy, PHE885 will be infused (in the outpatient or inpatient setting per physician discretion) as a single dose of 5.0×106 (range, 4×106 to 5×106) CAR-positive viable T cells. Each pt will be monitored 24 months post-infusion. Pts who will complete their Month 24 visit before the study ends will be followed yearly until the end of the study. Pts will be followed for up to 15 years after infusion in a separate protocol. Results: The primary endpoint is the best overall response (BOR) per independent review committee using the IMWG criteria. The summary measure is ORR, defined as the proportion of pts in the efficacy analysis set with a BOR of PR or better. Secondary endpoints include complete response rate, duration of response, PFS, OS, rate and durability of minimal residual disease negativity, safety, and cellular kinetics. An exploratory objective of the study is the assessment of CRS symptoms using a non-invasive biosensor patches (made of lightweight, water-resistant material that continuously take several vital sign parameters). Image:Summary/Conclusion: This Phase II trial of PHE885 will help further determine efficacy and safety outcomes in pts with r/r MM who failed ≥3 prior lines of therapy. The trial will be initiated in February 2022 and is estimated to treat 100 pts across 40 trial sites.