TNB-383B receives Orphan Drug Designation from the U.S. FDA

On the 6^th November 2019, the United States (US) Food & Drug Administration (FDA) granted Orphan Drug Designation (ODD) to TNB-383B for the treatment of patients with multiple myeloma (MM). TNB-383B is a bispecific antibody (bsAb) targeting B-cell maturation antigen (BCMA) on MM cells and CD3 on T cells.¹

TNB-383B clinical trials

An open-label, phase I study (NCT03933735) of TNB-383B is currently ongoing:²

• Patients with relapsed/refractory MM (RRMM) who have received three or more prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody (mAb) are being enrolled
• Design: two arms:
  • Arm A: monotherapy dose escalation
    • Aim: evaluate safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of single agent TNB-383B
    • Doses: 25mg–40mg, once every three weeks
      • TNB-383B will be administered in increasing doses until the maximum tolerated dose (MTD) is reached or recommended phase II dose (RP2D) is identified
    • Patients: ~24
  • Arm B: monotherapy dose expansion
    • Aim: evaluate safety, tolerability, PK and PD profiles of the MTD or RP2D
    • Patients: ~48
• Primary outcomes:
  • Number of subjects with dose-limiting toxicities
  • Number of subjects with adverse events (AEs) or serious AEs
  • Maximum observed plasma concentration of TNB-383B (C_max)
  • Area under concentration versus time curve from time zero to last quantifiable time point prior to next dose
  • Apparent terminal half-life of TNB-383B

Conclusion

bsAbs are a hot topic within the field of hematological malignancies. As bsAbs are designed to redirect immune effector cells to tumor cells, they are being investigated as agents to control the underlying hematological malignancy prior to allogeneic stem cell transplantation, with the aim of lowering relapse rates post-transplant. However, this redirection can lead to toxicity that must be carefully managed.³

Within the field of MM, several bsAbs are under investigation, including AMG 420 which also targets BCMA and CD3. The results of a phase I trial (NCT02514239) of AMG 420 in patients with RRMM were recently presented by Max Topp, University of Würzburg, Würzburg, DE, at the American Society of Clinical Oncology (ASCO) annual meeting.⁴ It remains to be seen whether AMG 420, TNB-383B, and other bsAbs will prove to be clinically efficacious, and where they may fit within the treatment pathway.

Read more about bsAbs for the treatment of MM, lymphoma, and acute myeloid leukemia (AML), here.