On June 4, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing a novel class of T cell engagers, reported interim data from the ongoing dose-escalation portion of a Phase 1/2a trial for HPN424 in patients with metastatic castration-resistant prostate cancer (mCRPC) at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Harpoon Therapeutics, JUN 4, 2021, View Source [SID1234583553]). HPN424 targets prostate-specific membrane antigen (PSMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells.

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As of April 23, 2021, the data cutoff date for the ASCO (Free ASCO Whitepaper) presentation, 89 patients have been dosed across 13 cohorts at fixed doses of 1.3 to 160 ng/kg and in step dosing cohorts up to 300ng/kg administered as a weekly intravenous infusion. These interim data demonstrated:

HPN424 was active and generally well tolerated
Antitumor activity included a confirmed PR per RECIST, PSA declines and circulating tumor cell (CTC) reductions
Treatment duration > 24 weeks observed in 15 of 74 (20%) pts, including 8 of 17 (47%) chemo-naïve patients
Cytokine release syndrome (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
"These encouraging data for HPN424 are continuing to show clinical activity, target engagement, and a manageable safety profile in this heavily pretreated patient population," stated Jerry McMahon, Ph.D., President and CEO, Harpoon Therapeutics. "As our step dose cohorts continue to enroll patients, we believe we are nearing the dose we intend to explore in the first expansion cohort that we plan to initiate this year."

"We are excited to share this clinical update from our HPN424 clinical trial. These data suggest that HPN424 is active and that the expected cytokine-mediated adverse events can be managed," said Natalie Sacks, M.D., Chief Medical Officer of Harpoon. "Our goal is to develop an effective immunotherapy treatment option for patients with prostate cancer."

Trial Design and Interim Results from the HPN424 Phase 1/2a Clinical Trial

This Phase 1/2a trial is a multicenter, open-label study designed to evaluate the safety, tolerability, pharmacokinetics and activity of HPN424 in patients with mCRPC who are progressing at the time of enrollment and have had at least two prior systemic treatments for metastatic disease. The initial ongoing phase of the trial is dose escalation, with the goal of determining a recommended dose for the expansion phase. The escalation phase began with single patient cohorts and transitioned to a 3×3 design when Grade 2 toxicity was observed. A step dosing regimen was introduced in December 2020. HPN424 is being administered to patients once weekly by intravenous infusion and the primary outcome measures are an assessment of safety and tolerability, pharmacokinetics, and pharmacodynamics. Secondary endpoints include duration of response, progression free and overall survival. Tumor assessments include PSA, CT and bone scans performed every 9 weeks.

As of the April 23, 2021 cut-off date, 89 patients have been treated in 13 cohorts with fixed doses ranging from 1.3 to 160 ng/kg and step dosing up to 300ng/kg using various regimens. Enrolled patients had a median of 5 prior therapies, including 73% with prior chemotherapy, and a median of two prior novel hormonal agents. Median PSA level was 129, with a range of 0.1-5000 ng/ml. The most frequent adverse events were cytokine release syndrome (CRS) ((all grade n=61 (69%), grade >3 n=4 (4%)), chills ((all grade n=60 (67%), grade >3 n=0 (0%)), and pyrexia ((all grade n=58 (65%), grade >3 n=2 (2%)). The majority of CRS events occurred with the first dose.

Dose Limiting Toxicities (DLTs) were observed at doses ranging from 96 to 300ng/kg and did not limit escalation and Maximum Tolerated Dose has not been reached. The most common DLTs were Transaminitis G4 (n=6) and Cytokine Release Syndrome G3 (n=4). The most common reason for study discontinuation was progressive disease; two of 89 (2%) patients discontinued treatment due to treatment-related AEs.

HPN424 demonstrated dose proportional increase in Cmax and AUC. Reduction in CTCs was seen in 36 of 64 (56%) patients with available baseline and on-treatment CTC counts. 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. A confirmed PR was observed in a patient treated at 160 ng/kg and that patient remains on study at 41 weeks.

Patients continue to be enrolled in the escalation and step dosing phase of the trial, with a goal to identify a dose for an expansion phase. The expansion phase of the trial will further evaluate the safety and activity of HPN424 in patients with mCRPC. This trial is titled, "Study of HPN424 in Patients with Advanced Prostate Cancer". For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT03577028.

Conference Call and Webcast Today

Harpoon’s management will host a webcast and conference call at 4 p.m. ET / 1 p.m. PT on Friday, June 4, 2021 to review the data and provide an update on other pipeline programs. The live call may be accessed by dialing 866-951-6894 for domestic callers or 409-216-0624 for international callers and using conference ID # 2657278.

A live webcast of the call will be available from the Events and Presentations section of the company’s website at View Source and will be archived there shortly after the live event.