Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma.

Abstract

8505 Background: JNJ-68284528 (JNJ-4528) is a chimeric antigen receptor T (CAR-T) cell therapy containing 2 BCMA-targeting single-domain antibodies. Here we present updated CARTITUDE-1 (NCT03548207) phase 1b results with longer follow-up. Methods: Pts had MM per IMWG criteria, measurable disease, received ≥3 prior regimens or were double refractory to a PI and IMiD, and received anti-CD38 antibody. Cyclophosphamide 300 mg/m2+ fludarabine 30 mg/m2 over 3 days were used for lymphodepletion. JNJ-4528 (median, 0.73x106 CAR+ viable T cells/kg) was given as a single infusion. Cytokine release syndrome (CRS) was graded by Lee et al2014 and neurotoxicity by CTCAE, v5.0 and ASTCT grading. Response was assessed per IMWG criteria. Results: As of 17 Jan 2020, median follow-up is 9 mo (3–17). Phase 1b enrollment is complete (N = 29 treated; median 5 (3–18) prior lines, 76% penta-exposed, 86% triple-refractory, 31% penta-refractory, 97% refractory to last line of therapy). Most frequent adverse events (AEs) were neutropenia (100%), CRS (93%), and thrombocytopenia (93%). Grade (Gr) ≥3 hematologic AEs were neutropenia (100%), thrombocytopenia (69%), and leukopenia (59%). 27 (93%) pts had CRS; 25 Gr 1–2, 1 Gr 3, and 1 Gr 5 (day 99 subsequent to dose-limiting toxicity of prolonged Gr 4 CRS). Median time to onset of CRS was 7 days (2–12). 4 pts had treatment-related neurotoxicity: 3 Gr 1–2 and 1 Gr 3. ORR was 100%, with 22 (76%) stringent complete responses (sCRs), 6 (21%) very good partial responses (VGPRs), and 1 (3%) PR. Median time to ≥CR was 2 mo (1–9). 26/29 pts are progression-free, with 6-mo progression-free survival rate of 93% and longest response ongoing at 15 mo. 1 death due to CRS and 1 to acute myeloid leukemia (not treatment-related) occurred during the study. All 16 pts (14 sCR, 2 VGPR) evaluable at 6 mo were minimal residual disease negative at 10−5 or 10−6. JNJ-4528 CAR+ T cell expansion peaked between day 10–14. At 6-mo individual follow-up, 22/28 pts had JNJ-4528 CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood, suggesting CAR-T persistence in peripheral blood did not seem to correlate with deepening of response. At peak expansion, preferential expansion of CD8+ CAR-T cells with a central memory phenotype was observed in peripheral blood. Conclusions: JNJ-4528 treatment led to responses in all pts. These responses were early, deep, and durable at a low dose of CAR-T cells with 26/29 (90%) pts progression free at median 9-mo follow-up. CRS was manageable in most pts, supporting outpatient dosing. Clinical trial information: NCT03548207 .