On May 26, 2022 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported interim safety and efficacy data from the ongoing dose escalation and expansion study evaluating HPN328, Harpoon’s half-life extended TriTAC targeting delta-like canonical Notch ligand 3 (DLL3), for the treatment of SCLC and other neuroendocrine cancers (Press release, Harpoon Therapeutics, MAY 26, 2022, View Source [SID1234615193]). The first scientific presentation of these interim data will be featured in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2022, taking place in Chicago from June 3-7.
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The encouraging interim results, as of the data cut-off date of April 21, 2022, showed that HPN328 demonstrated anti-tumor activity and a favorable safety profile in patients with SCLC, neuroendocrine prostate cancer and other neuroendocrine cancers. Seven of 18 patients (39%) had a decrease in sum of target lesion diameters, with 3 of 11 patients (27%) with SCLC across all dose cohorts experiencing a greater than 30% decrease in sum of target lesion diameters. Additionally, 4 of 6 patients (67%) with SCLC treated at greater than or equal to 1.215mg/week experienced a decrease in sum of target lesion diameters. To date, there have been no dose-limiting toxicities observed and no discontinuations due to adverse events. Grade 1-2 CRS occurred in 22% of patients. No grade 3 or higher CRS or any immune effector cell associated neurotoxicity syndrome (ICANS) events have been observed.
"DLL3 is expressed on the surface of tumor cells in more than 70% of small cell carcinomas, including small cell lung cancer, neuroendocrine prostate cancer, and other small cell neuroendocrine cancers, and HPN328 is specifically engineered to hit this target," said Himisha Beltran, M.D., of Dana-Farber Cancer Institute, Boston, a Principal Investigator in this study. "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. I look forward to the clinical results from further investigations with this promising drug candidate."
To date, study investigators have observed 1 confirmed partial response with a 53% decrease in sum of target lesion diameters at week 10 in a patient with SCLC who previously achieved a best overall response of stable disease on platinum-based chemo-immunotherapy. Another SCLC patient treated with 3 prior lines of therapy achieved a 65% decrease in sum of target lesion diameters with deepening of target lesion response, with treatment ongoing beyond six months. There were 6 instances of patients with best overall response of stable disease (4 SCLC, 1 neuroendocrine prostate cancer, and 1 thymic atypical carcinoid).
"We are pleased to share our continued progress with the HPN328 anti-DLL3 T cell engager clinical program and these interim data in a peer-reviewed setting, providing further clinical validation for our TriTAC technology in solid tumors," said Julie Eastland, President and CEO of Harpoon Therapeutics. "Given the clinical activity and acceptable tolerability profile observed to date, we look forward to continuing dose escalation, with the goal of identifying a dose for expansion studies by the end of the year, as we further explore the full potential of HPN328 as both a single agent and in future combination studies with atezolizumab to help patients with cancer."
Details of the ASCO (Free ASCO Whitepaper) poster presentation are as follows:
Title: Interim results of an ongoing phase 1/2a 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
Abstract/Poster: 8566/193
Session Title: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Session Date and Time: Monday, June 6, 8:00 a.m. to 11:00 a.m. CT
About HPN328
HPN328, a Tri-specific T cell Activating Construct (TriTAC), is being evaluated as monotherapy in an ongoing open-label, multicenter two-part study to assess the safety, tolerability and pharmacokinetics in patients with advanced cancers associated with expression of DLL3. Part 1 of the study is designed to determine dosage(s) for further evaluation in expansion cohorts during Part 2.
In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to HPN328 for the treatment of SCLC.
For additional information on the HPN328 clinical study, please go to ClinicalTrials.gov and use Identifier NCT04471727.