HPN424-PSMA T Cell Engagers for Metastatic Prostate Cancer

HPN424 is a prostate-specific membrane antigen (PSMA)- targeting T cell engager, engineered with three binding domains:
• PSMA (for tumor binding)
• Albumin (for half-life extension)
• CD3 (for T cell engagement)
HPN424 is constructed as a small, globular protein (~50kDa) to enable efficient solid tumor penetration with prolonged half-life and excellent stability. HPN424 is designed to bind monovalently to CD3 and PSMA, minimizing non-specific T-cell activation.

Harpoon Therapeutics is currently conducting a "Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN424 in Patients With Advanced Prostate Cancer Refractory to Androgen Therapy"

As of May 31, 2021, the data cutoff date for the Company’s HPN424 presentation, the Company updated the ASCO interim data to describe newly enrolled patients and additional follow-up on existing patients already enrolled in the 300 ng/kg step dose cohort. The company has examined several step dosing regimens in this cohort and had the following observations:
  • Eight patients most recently enrolled in this cohort were treated with the same modified step dose regimen. Preliminary data from these patients include 3/8 (38%) with PSA declines that occur early in the course of treatment.
  • For the total 19 patients enrolled in this cohort, 4/19 showed PSA declines, including two patients with PSA30.
  • Anti-Tumor Activity: Treatment duration of >24 weeks in 20% of patients, Confirmed RECIST PR, PSA declines and CTC reductions observed across cohorts
  • Fifteen of 74 (20%) pts with >1 post-baseline value had PSA decreases from baseline ranging from -2% to -76%, including 4 pts with PSA50 response and 2 pts with PSA30 response
  • Treatment duration > 24 weeks observed in 15 of 74 (20%) pts, including 8 of 17 (47%) chemo-naïve patients
  • Reduction in CTCs was seen in 36 of 64 (56%) patients with available baseline and on-treatment CTC counts
  • CRS has been transient and manageable with 4% of patients experiencing Grade 3 CRS
  • CRS and transaminitis events observed most often in Cycle 1, with diminished frequency and severity in subsequent cycles
  • Introduction of step dose regimens has allowed for the administration of higher target doses, currently at 300ng/kg
Next Step: Assessment of optimal target dose and patient population for expansion ongoing
Source: www.harpoontx.com