FDA Grants Orphan Drug Designation to BCMA-Targeted TriTAC HPN217 for Myeloma

January 13, 2021 — The FDA has granted an orphan drug designation to the BCMA-targeted trispecific T-cell activating recombinant protein construct as treatment for patients with multiple myeloma.

The FDA has granted an orphan drug designation to the BCMA-targeted trispecific T-cell activating recombinant protein construct (TriTAC) as treatment for patients with multiple myeloma, according to an announcement from Harpoon Therapeutics, Inc.1

The agent is currently under exploration in a multicenter, open-label, phase 1/2 trial (NCT04184050), which was designed to examine the safety, tolerability, pharmacokinetics, and activity of HPN217 in patients with relapsed/refractory multiple myeloma.2

“Orphan drug designation for multiple myeloma represents a significant milestone in the development of HPN217 and recognizes its potential to address a significant unmet medical need for the patients suffering from this condition,” Jerry McMahon, PhD, president and chief executive of Harpoon Therapeutics, stated in a press release. “I am pleased with the clinical progress we are making with this program and we are planning to present interim data from the ongoing phase 1/2 dose-escalation trial later this year.”

BCMA is expressed on B lineage cells such as memory B cells, plasmablasts, and plasma cells.3 It is known that the BCMA ligands TNFSF13/APRIL and TNFSF13B/BAFF activate the MAP kinase and BcL-2/XL pathways to encourage proliferation and survival and that BCMA expression is upheld after plasma cell transformation into myeloma. As such, BCMA is under exploration as an important target for several therapies that are being developed to combat this disease. 

One such therapy is the novel BCMA-targeted TriTAC, which was designed to have a long circulating half-life and to redirect T cells so that they would eliminate BCMA-positive cancer cells.

In ongoing phase 1/2 trial examining the agent is comprised of 2 parts. In the phase 1, dose-escalation portion of the research, investigators seek to identify the recommended phase 2 dose (RP2D) for HPN217 in patients with relapsed/refractory disease. In the phase 2 portion, they will further examine the safety and efficacy of the agent.

To be eligible for enrollment, patients must have received 3 or more previous therapies, have measurable disease, and an ECOG performance status of 0-2, as well as acceptable hematologic status, renal function, and hepatic function. If they had previously received a BCMA-targeted agent or concurrent treatment with antitumor necrosis factor alpha therapies, systemic corticosteroids, or other immunosuppressive agents within 2 weeks before screening, they were excluded.

In the trial, patients will receive HPN217 once weekly via intravenous infusion. The co-primary objectives of the research are assessment of adverse effects, to determine the maximum-tolerated and RP2D, and to characterize the pharmacokinetics of the agent. Key secondary objectives are to identify efficacy of the agent using International Myeloma Working Group criteria and to determine immunogenicity information by examining antidrug antibodies.

In April 2020, the first patient had been dosed with the BCMA-targeted TriTAC.4 Thus far, the agent has been found to be well tolerated. Notably, as of the December 1, 2020 data cutoff date, no dose-limiting toxicities have been reported with the drug. 

The interim data from the trial is anticipated to be presented this year, with the dose-expansion portion of the research launching in the second half of 2021, according to the pharmaceutical company.


  1. Harpoon Therapeutics granted orphan drug designation from FDA for HPN217 for treatment of multiple myeloma. News release. Harpoon Therapeutics, Inc. January 13, 2021. Accessed January 13, 2021. http://bit.ly/3i8tFog.
  2. A phase 1/2 open-label, multicenter, dose escalation and dose expansion study of the safety, tolerability, and PK of HPN217 in patients with R/R MM. ClinicalTrials.gov. Updated July 14, 2020. Accessed January 13, 2021. https://clinicaltrials.gov/ct2/show/NCT04184050.
  3. Law C-L, Aaron W, Austin R, et al. Preclinical and nonclinical characterization of HPN217: a tri-specific T cell-activating construct (TriTAC) targeting B cell maturation antigen (BCMA) for the treatment of multiple myeloma. Presented at: 2018 ASH Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 3225. https://bit.ly/3nA4ts4.
  4. Harpoon Therapeutics doses first patient with HPN217, a BCMA targeting TRITAC, for multiple myeloma. News release. Harpoon Therapeutics, Inc. April 27, 2020. Accessed January 13, 2021. http://bit.ly/3oGjcTL.