FDA Grants Fast Track Designation to HPN217 for R/R Multiple Myeloma

The FDA has granted fast track designation to the novel BCMA-targeting agent HPN217, for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 4 lines of therapy, according to a press release by Harpoon Therapeutics.¹

An investigation of the safety, tolerability, and pharmacokinetics of HPN217 is underway in a phase 1/2 clinical trial (NCT04184050). Recent findings from an interim analysis of the study showed HPN217 to be safe when administered up to a 2150-µg weekly dose. The treatment-emergent adverse events (TEAEs) were considered to be transient and manageable.^1,2

“We are pleased that HPN217 has received FDA fast track designation because it highlights the serious unmet medical need for patients with relapsed, refractory multiple myeloma who received multiple lines of therapy,” stated Julie Eastland, president, and chief executive officer, Harpoon Therapeutics, in a press release. “We are focused on selecting an initial dose to study in the expansion phase of the ongoing phase 1/2 clinical trial in the first half of this year as we progress HPN217 forward as an innovative new treatment option for these patients.”

In the open-label, multicenter, dose-escalation, and dose-expansion study, 114 patients will be enrolled in either portion of the study to receive intravenous HPN217 once weekly for an hour. Patients enrolled will be evaluated for the coprimary end points of assessment of adverse events (AEs), estimation of the maximum-tolerated dose, determination of the recommended phase 2 dose, and characterization of pharmacokinetics of serum levels. Secondary end points of the study include efficacy determined by responses, and the immunogenicity of HPN217.³

Twenty-two patients were included in the interim analysis and treated in 8 individual cohorts, at 2150 µg/week. There were no dose-limiting toxicities observed in the study and the MTD had not yet been reached. The most common TEAEs observed during the analysis were anemia, neutropenia, and thrombocytopenia. No cases of cytokine release syndrome were seen among the 7 patients treated with 5–270 µg/week of HPN217. Among the 15 patients treated with ≥ 810 µg/week of HPN217, 4 patients developed CRS.²

Patients are eligible to enroll in the ongoing study given they are 18 years of age or older with documented relapsed/refract multiple myeloma. All patients are required to have received at least 3 prior therapies including a proteasome inhibitor, immune-modulatory drug, and an anti-CD38 antibody. No patient can be a candidate for or be intolerant of all established therapies known to provide clinical benefit in multiple myeloma and all patients must have measurable disease. The final inclusion requirement is that any acute effects due to any prior therapy be resolved to a grade 1.³

The study excludes patients with plasma cell leukemia, non-secretory myeloma, and patients with only extramedullary relapse of multiple myeloma who do not meet the requirement for measurable disease. Individuals with prior autologous peripheral stem cell transplant or prior autologous bone marrow transplantation within less than 90 days of the start of study are ineligible to enroll as are those who had prior allogeneic stem cell transplantation or solid organ transplantation within 12 months of study screening, and those whose last anticancer treatment occurred within 2 weeks of scheduled dosing in the study.

Currently, patients are being recruited in Arizona, California, Colorado, Kansas, New York, Oregon, and Washington. Outside of the United States, patients were being recruited in France, Germany, and Spain.

With a fast track designation, the FDA will help guide the development process for HPN217 in relapsed/refractory multiple myeloma considering its potential to fill an unmet medical need. Further, any application submitted to the FDA may be expedited.¹