Initial data from the phase I study of CART-ddBCMA

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, new data were released from the phase I study of CART-ddBCMA for patients with relapsed/refractory multiple myeloma (NCT04155749).¹ CART-ddBCMA has been granted fast track designation, orphan drug designation, and regenerative medicine advanced therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory multiple myeloma.²

CART‑ddBCMA is an autologous CAR T-cell therapy, with a novel synthetic protein-binding domain. It has been designed to be stable at high temperatures and to reduce the risk of immunogenicity, with potential to alter the binding surface to allow different degrees of affinity. In addition, CART‑ddBCMA is reportedly easy to manufacture, producing a high yield, with a median of 99% viable cells.¹

Study design

This phase I study is a multi-center, dose escalation trial for patients with relapsed/refractory multiple myeloma who had previously received ≥3 regimens.¹ Patients receive a single dose of either 100 × 10⁶ CART-ddBCMA (DL1) or 300 × 10⁶ CART-ddBCMA (DL2), following fludarabine and cyclophosphamide at Days −5 to −3.¹ The primary endpoint was the incidence of treatment-emergent adverse events and dose-limiting toxicities, as well as to identify the recommended dose for phase II trials³. Other endpoints included best response, duration of response, presence of minimal residual disease, and progression-free and overall survival.⁴

Patient characteristics and results¹

Of the 31 patients dosed with CART‑ddBCMA (25 in DL1 and 6 in DL2 as of May 3, 2022):

• Median patient age was 66 years (44–76 years)
• Median prior lines of therapy was 5 (3–16)
  • 77% of patients had triple-refractory disease (n = 24)
  • 68% of patients has penta-refractory disease (n = 21)
• 39% of patients had extramedullary disease at the time of treatment (n = 12)
• Cytokine release syndrome occurred in 28 patients
  • 1 patient experienced Grade 3 cytokine release syndrome
• Immune effector cell-associated neurotoxicity syndrome (ICAN) occurred in 7 patients
  • 5 patients experienced Grade 1/2 ICAN
  • 2 patients experienced Grade 3 ICAN
• The overall response rate was 100%
• A total of 71% of patients achieved a complete response or a stringent complete response, and 94% of patients achieved a very good partial response or better

Conclusion

Triple-refractory multiple myeloma currently lacks effective treatment options; hence novel targets and agents are being explored for this population. The 100% overall response rate¹ reported in this study demonstrates that CART-ddBCMA has potential for use in heavily pretreated and refractory disease, with a low incidence of adverse events and toxicities reported so far. This trial is limited by the small sample size, and further studies with larger cohorts will provide a better understanding of the efficacy and safety of this cell therapy. The maximum tolerated dose was not reached in this study; however, the second phase of this study is expected to begin later this year,¹ and will provide more data on the optimum dose for this drug.