Harpoon Presents Interim Data of T-Cell Engager HPN328 Clinical Trial

Harpoon Therapeutics has announced updated interim efficacy and safety data from its ongoing dose escalation study of HPN328 in small cell lung cancer (SCLC) and other neuroendocrine cancers at the American Society of Clinical Oncology annual meeting 2022.¹

The drug, HPN328, was previously granted orphan drug designation for the treatment of SCLC. It targets DLL3, using Harpoon Therapeutics’ half-life extended TriTAC, which mitigates cytokine release syndrome (CRS) while maintaining clinical activity.¹

“DLL3 is expressed on the surface of tumor cells in more than 70% of small cell carcinomas, including SCLC, neuroendocrine prostate cancer, and other small cell neuroendocrine cancers, and HPN328 is specifically engineered to hit this target,” Himisha Beltran, MD, of Dana-Farber Cancer Institute, said in a statement.²

“The encouraging single-agent clinical activity observed to date in patients that have received multiple prior lines of therapy, combined with the favorable safety profile, suggest the investigational T-cell engager HPN328 may offer meaningful clinical benefits as a monotherapy for patients expressing DLL3,” Beltran said.²

HPN328 has 3 binding domains, including anti-albumin, anti-CD3, and anti-DLL3, which help kill DLL3 cancer cells and redirect T cells.¹

In the trial, investigators targeted individuals with relapsed SCLC after platinum chemotherapy or those with other malignancies with high-grade neuroendocrine that is relapsed or refractory to standard of care or when no standard of care is available.¹

Investigators assessed the safety and tolerability of the drug, as well as the maximum dose tolerated. Additionally, they aimed to characterize the drug’s pharmacodynamics and pharmacokinetics and evaluate the preliminary anti-tumor activity.¹

The median half-life for the drug was 71 hours, and it showed linear pharmacokinetics with dose-proportional increases in exposures at 0.135 mg to 12 mg.¹

The drug was given once a week via intravenous infusion, and individuals were premedicated with acetaminophen, dexamethasone, and histamine receptor blockers at the initial dose. The individuals in the study were also imaged every 9 weeks and had retrospective analysis of tumor tissue for DLL expression. The study included a total of 18 individuals who were treated with HPN328.¹

Investigators found that HPN328 was clinically active and well tolerated. They observed T-cell margination and activation was consistent with target engagement.¹

The drug showed anti-tumor activity. Three of the 11 individuals with SCLC had greater than a 30% decrease in the sum of target lesion diameters, including 1 confirmed partial response.¹

Additionally, 4 of 6 of individuals with SCLC who were treated with 1.215 mg/week or more had a decrease in the sum of target lesion diameters.¹

Investigators also reported that 6 of 18 of the individuals had the best overall response of stable disease.¹

Treatment duration of 20 or more weeks was observed in 6 of 18 of the individuals. Investigators also observed that CRS was manageable, with 22% of individuals experiencing grade 1 or 2 CRS. No grade 3 or greater CRS occurred.¹

Furthermore, the dose escalation is ongoing, and a maximum-tolerated dose has not yet been reached, according to the poster presentation.¹

No dose limiting toxicities were observed.¹

Additionally, no individuals discontinued the study because of adverse events (AEs).¹

Approximately 83% of individuals experienced treatment-related AEs in any grade, but just 1 experienced any treatment-related AE that was grade 3 or greater.¹

Common treatment-emergent AEs included chills, constipation, dysgeusia, fatigue, hypotension, and vomiting.¹

The duration of treatment ranged from 4.1 to 41.4 weeks, and step-dosing was initiated for target doses higher than 3.6 mg/week.¹

The highest target dose evaluated to date was 12 mg/week.¹

Reference

1. Johnson M, Dy G, Mamdani H, Dowlati A, et al. Interim results of an ongoing Phase 1/2 study of HPN328, a tri-specific half-life extended DLL3-targeting T-cell engager, in patients with small cell lung cancer and other neuroendocrine cancers. Presented June 6, 2022. Accessed May 25, 2022. Email.

2. Harpoon presents interim data from ongoing dose escalation portion of T-cell engager HPN328 clinical trial at 2022 ASCO Annual Meeting. Harpoon Therapeutics. May 26, 2022. Accessed May 26, 2022. Email.