HPN536 Trispecific T Cell Engagers Mesothelin Associated Cancer

HPN536 is a novel, MSLN targeted, trispecific, T-cell–activating protein construct that can potently redirect T cells to lyse tumor cells and was remarkably well tolerated in nonhuman primates at single doses up to 10 mg/kg, which is far above the expected therapeutic dose level.

Harpoon Therapeutics are conduction "A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression Who Have Failed Standard Available Therapy"

The objective of the trial is to
-assess safety and tolerability at increasing dose levels 
- Pharmacokinetic and pharmacodynamic data 
‐ Evaluate preliminary anti-tumor activity

Dosing has occurred across 10 fixed-dose cohorts of 6 to 560ng/kg and three step dose cohort up to 1200ng/kg, with total enrollment of 60 patients. Tumor types treated include late-stage ovarian (47%), pancreatic (40%) and peritoneal and pleural mesothelioma (13%) cancers. Pharmacokinetic analysis shows median half-life of more than 70 hours for HPN536. Among the relapsed/refractory ovarian cancer patients with at least one post-baseline scan, 11 of 20 (55%) patients showed stability of target lesions, including three patients with target lesion shrinkage. In addition, five of 27 (19%) ovarian cancer patients had a duration of treatment of greater than 24 weeks. One event of CRS (Grade 3) occurred at 54ng/kg in the absence of dexamethasone premedication. The CRS event resolved and patient was successfully re-treated.


Next Step:

Anticipated expansion cohort initiation & Phase 1 data presentation by end of year 2021