S827 CLINICAL RESPONSES AND PHARMACOKINETICS OF FULLY HUMAN BCMA TARGETING CAR T CELL THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA

Abstract

Background:Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who receive high‐dose BCMA‐targeting CAR‐T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re‐infusion of CAR‐T cells is not effective. To solve this dilemma, we have developed a novel BCMA‐targeting CAR‐T (CT103A) with a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4–1BB co‐stimulatory and CD3z activation domains.Aims:The primary objectives are to characterize the safety and tolerability in patients with R/R MM. The secondary objectives include evaluation of anti‐myeloma activity, cytokines, CAR‐T cell persistence, and pharmacokinetics.Methods:ChiCTR1800018137 is a single‐center and single‐arm trial of CT103A in patients with RRMM. Between September 21, 2018, and January 21, 2019, nine patients (including 3 patients having relapsed after being given a murine BCMA CAR‐T) received CT103A in 3+3 dose‐escalation trial (three doses at 1, 3, 6 × 106/kg) after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. All Patients had received a median of 4 prior lines (range 3 ‐ 5) of MM therapy.Results:At the time of the February 4, 2019 data analysis, the overall response rate was 100% (Table1), and all patients had a rapid response within 14 days, with 67% (2/3) reaching CR/sCR at the lowest dose. The pharmacokinetics of CT103A were assessed by a digital polymerase chain reaction. Robust expansions were seen even at the lowest dosage level. In addition, Cmax and AUC0‐28 reached levels comparable to reported CD19 CAR‐T. In the first two dose groups, the grade of cytokine release syndrome (CRS) was 0 ‐ 2. In the 6 × 106 /kg dose group, DLT had been observed in one patient.Summary/Conclusion:Data from this early‐stage clinical study showed the unparalleled safety and efficacy of CT103A. Major AEs were transient, manageable, and reversible. three patients who relapsed the murine BCMA CAR‐T were treated with CT103A, two patients achieved CR, and one patient achieved VGPR. 100% ORR and a rapid response within 2 weeks, suggests CT103A could be developed as a competitive therapeutic to treat patients with RRMM.image