Three-Year Follow-up on Efficacy and Safety Results from Phase 1 Lummicar Study 1 of Zevorcabtagene Autoleucel in Chinese Patients with Relapsed or Refractory Multiple Myeloma

Introduction: Phase 1b of LUMMICAR STUDY 1 was conducted in China (NCT03975907) for zevorcabtagene autoleucel (zevor-cel, CT053), a fully human autologous chimeric antigen receptor (CAR) T-cell therapy comprising a B-cell maturation antigen-specific single-chain variable fragment, in patients with relapsed or refractory multiple myeloma (RRMM). Previously disclosed 1-year follow-up data (ASH 2021 Abstract 2821) demonstrated a tolerable safety profile and deep and durable responses in 14 patients. Here, we present the updated results with 3 years of follow-up after the last patient was infused.

Methods: Patients were eligible to be enrolled with a diagnosis of RRMM, ECOG score of 0 or 1, and they had received at least 3 prior regimens including at least one proteasome inhibitor and one immunomodulatory drug. A single infusion of zevor-cel (two dose levels, 100 × 10⁶ CAR⁺ T cells and 150 × 10⁶ CAR⁺ T cells) was administered 5–7 days after the start of lymphodepletion. Response was assessed by investigator per IMWG 2016 criteria. Bone marrow aspirates were tested for minimal residual disease (MRD) by the EuroFlow assay with a minimum sensitivity of 1 in 10⁵ nucleated cells.

Results: Starting July 23, 2019, 14 patients with a median age of 54 years (range 34, 62), received a single infusion of zevor-cel (100 × 10⁶ CAR⁺ T cells in 3 patients, 150 × 10⁶ CAR⁺ T cells as the recommended phase 2 dose in 11 patients). The median number of prior lines of therapy was 6. A total of 50.0% of the infused patients had high-risk cytogenetics, 14.3% had extramedullary disease, 14.3% had ISS stage III, and no patients received bridging therapy.

By the data cutoff date (July 17, 2023), the median survival follow-up duration was 37.7 months (range:14.8, 44.2). Overall response rate was 100% (95% CI 76.8, 100.0), in which 11 (78.6%) patients achieved complete response (CR) or stringent complete response (sCR); 2 (14.3%) patients achieved very good partial response and 1 (7.1%) patient had partial response. All patients who achieved CR or better were MRD negative. The median progression-free survival was 25.0 months (14.9, not evaluable [NE]) for all patients and 26.9 months (15.5, NE) for patients with sCR/CR (Figure 1A). The median duration of response was 24.1 months (14.0, NE) for all patients and 26.0 months (14.6, NE) (Figure 1B) for patients with sCR/CR. At data cutoff, 5 subjects still had ongoing responses, and 7 patients progressed and were still in survival follow-up. Two patients had died at month 42.6 and 32.6, respectively, and their deaths were deemed unrelated to zevor-cel.

All patients experienced treatment related adverse events and grade 3 or 4 hematologic toxicity. Thirteen patients (92.9%) had cytokine release syndrome (all grade 1 or 2). No immune effector cell-associated neurotoxicity syndrome, no second primary malignancy, and no autoimmune disease were reported. All patients have been tested negative for replication competent lentivirus to date.

Conclusions: At approximately 3 years of follow-up, heavily pre-treated RRMM patients maintained deep and durable responses after receiving a single infusion of zevor-cel, which showed a well-managed safety profile in the ongoing long-term follow-up.