HPN217 is a BCMA-targeting tri-specific t-cell activating construct (TriTAC) in development for patients with multiple myeloma.

SparkCures ID 367
Developed By Harpoon Therapeutics
Generic Name HPN217
Treatment Classifications
  • Trispecific Antibody
Treatment Targets

Clinical Trials

Published Results

Updated Interim Results from a Phase 1 Study of HPN217, a Half-Life Extended Tri-Specific T Cell Activating Construct (TriTACĀ®) Targeting B Cell Maturation Antigen (BCMA) for Relapsed/Refractory Multiple Myeloma (RRMM)

December 11, 2022

As of June 27, 2022, 49 patients were treated with HPN217. The highest fixed-dose level administered was 2860 μg/wk. The highest step-dose level assessed was 12000 μg/wk, dose escalation in step-dose regimens is ongoing. Patients received a median of 6 prior systemic regimens (84% prior transplantation, 69% penta-exposed, 22% prior BCMA-targeted therapy). Median age (range) was 70 (38-78). Median duration of treatment is 10.1 weeks (0.1 – 64 weeks; patient at 64 weeks ongoing with a continued response). The most common (≥20%) treatment-emergent adverse events (TEAEs) were anemia (49%), fatigue (37%), CRS (25%), nausea (22%), arthralgia (20%), diarrhea (20%) and transaminitis (20%). All CRS events were G1-G2 (no ≥ G3 events reported). In step-dose regimens, all CRS events were G1. No events of Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported. Two dose-limiting toxicities (DLTs) of transaminitis were reported at 2860 μg/wk. No sequelae of liver failure were associated with these events. No DLTs have been reported in the step-dose regimen and the MTD has not been reached.

HPN217 continues to exhibit linear and dose proportional PK across dose levels with a median half-life of 66 h (range 26 to 197 h). Transient cytokine increases are higher with initial dosing compared to subsequent and step dosing. Patients with objectives responses (PR or better) have on treatment reduction in soluble BCMA, higher cytokine elevations and higher upregulation of the activation marker CD69 on CD8+ T cells.

Responses have been observed at all dose levels ≥ 2150 μg/wk. Dose escalation is continuing in step-dose regimens at 24000 μg/wk. Updated data including duration of response will be presented at the meeting.