CT103A, a novel fully human BCMA-targeting CAR-T cells, in patients with relapsed/refractory multiple myeloma: Updated results of phase 1b/2 study (FUMANBA-1).

8025 Background: CT103A, which is designed with a fully human BCMA-specific CAR structure, has shown sustained efficacy and durable safety in heavily pretreated relapsed and refractory multiple myeloma patients. Here, we report updated efficacy and safety data of its phase 1b/2 study (FUMANBA-1) with longer duration of follow-up. Methods: FUMANBA-1 is conducted in 14 centers in China. This study enrolled RRMM patients who received ≥ 3 lines of prior therapies containing at least a proteasome inhibitor and an immunomodulatory agent and were refractory to their last line of treatment. Patients who have progressed on previous BCMA CAR-T cell therapy were also included. All patients received a single infusion of CT103A at the dose of 1.0 x 10 6 CAR-T cells/Kg. The objective is to evaluate the efficacy, safety and PK/PD of CT103A. Results: As of the September 9 th , 2022, 103 patients [53.4% male; median age 58.0 years (range 39-70)] with RRMM received CT103A (17 in phase 1b; 86 in phase 2) with a median follow-up of 13.8 months (range 0.4 to 27.2). The treated patients had received a median of 4 (range 3-23) lines of prior therapy. 101 patients were evaluable for efficacy assessment. The median time to first response was 16 days (range 11-179). A 96% ORR was observed, with 74.3% ≥ CR. Median DOR and median PFS have still not reached. The 12-month PFS rate was 78.8% (95% CI: 68.6–85.97). For patients without prior BCMA CAR-T therapy (N = 89), ORR was 98.9% with 78.7% ≥ CR. For patients without prior BCMA CAR-T therapy and received CT103A for more than 6 months as of the cutoff date (N = 81), ORR was 98.8% with 80.2% ≥ CR. For patients with prior BCMA CAR-T cell therapy, 4/5 (80%) of those who achieved sCR still sustained sCR over 18 months post infusion. Of the 101 patients, 95% achieved MRD-negativity with a median time to MRD-negative of 14 days (range 13-185), and all patients with CR/sCR were MRD-negative. Furthermore, 82.4% (95%CI 70.90-89.72%) achieved sustained MRD negativity over 12 months. Since the previous publication in 64 th ASH meeting, no new events of CRS and ICANS occurred. The most common ≥ grade 3 treatment-related AEs were still hematologic. The expansion of CT103A reached the median peak level of 87570.6 copies/μg gDNA at a median of 12 days. CT103A was still above lower limit of qualification (100 copies/μg gDNA) in 50.0% (28/56) patients at 12 months and 40.0% (4/10) patients at 24 months after infusion. In addition, only 20 of 103 patients (19.4%) with evaluable samples were detected to be positive for the anti-drug antibody. Conclusions: At a longer median follow-up of 13.8 months, CT103A achieved deep and long-lasting responses in heavily pre-treated patients with MM. Furthermore, patients with prior BCMA CAR-T cell therapy who achieved sCR had sustained sCR over 18 months. CT103A demonstrated a favorable safety profile with no new risk observed with longer follow-up. Clinical trial information: NCT05066646 .