HARPOON THERAPEUTICS ANNOUNCES PRELIMINARY SAFETY AND PHARMACOLOGY DATA FROM ITS HPN424 PHASE 1 TRIAL IN PROSTATE CANCER
Initial data shows HPN424 serum exposure supports weekly dosing
Changes in blood-derived tumor cell and serum biomarkers consistent with T cell activation
HPN424 dose escalation proceeding to identify Phase 2 therapeutic dose
South San Francisco, CA – January 2, 2019 – Harpoon Therapeutics, Inc. (“Harpoon”), a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients with cancer and other diseases, today announced preliminary safety and mechanism of action findings from an ongoing Phase 1 clinical trial evaluating its lead compound, HPN424, in patients with progressive metastatic castration resistant prostate cancer (mCRPC). The Phase 1 trial is a multicenter, open-label dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and clinical activity of HPN424, a TriTAC (Tri-specific T Cell Activating Construct) that targets prostate-specific membrane antigen (PSMA), a clinically validated tumor antigen target in prostate cancer.
Eligible patients must have mCRPC, have received at least two prior treatment regimens for mCRPC, and have evidence of disease progression on the most recent systemic treatment regimen. Clinical observations from the first seven prostate cancer patients treated with HPN424 include:
Measurement of drug in the sera from patients indicates sufficient drug exposure during the treatment course to support once weekly dosing.
Measurable reduction in circulating tumor cells (CTC) in three of four patients evaluated as a biomarker for PSMA target engagement.
Dose-dependent, transient increase in peripheral cytokine and chemokine levels, consistent with the expected T cell activation mechanism of action.
No dose limiting toxicities have been observed to date, with four dose levels tested.
Adverse events were consistent with the expected mechanism of action, with three patients reporting grade 2 rigors or fevers that were manageable. A grade 3 cytokine release syndrome (CRS) event was reported in one patient from the fourth cohort but resolved within eight hours. All patients experiencing adverse events were successfully re-treated after one week without further complications.
All seven patients remain on study with weekly treatment of HPN424. Three patients have been analyzed for disease burden using computed tomography scans, bone scans and measurement of prostate serum antigen levels. To date, two patients have shown stable disease and one patient exhibited unconfirmed progressive disease and continues on study. The other four patients are early in their treatment and have not yet been evaluated for disease burden.
“These initial results in advanced metastatic castration resistant prostate cancer patients suggest that HPN424 is activating T cells in a manner that is consistent with tumor target engagement,” said Natalie Sacks, M.D., Chief Medical Officer of Harpoon. Dr. Sacks added, “We have observed early signals confirming the mechanism of action of HPN424, and have obtained encouraging safety data that supports continued dose escalation to define a Phase 2 therapeutic dose and regimen.”
“These results provide the first clinical evidence suggesting Harpoon’s TriTAC platform is performing as designed, by activating T cells in a target-dependent manner and by showing evidence of sufficient drug exposure during the treatment course to support once weekly dosing,” said Holger Wesche, Ph.D., Chief Scientific Officer of Harpoon. “HPN424 is a novel T cell biologic that has been designed to deliver potent T cell killing to PSMA-expressing tumor cells. We are encouraged by the early human safety and pharmacology data emerging from our Phase 1 trial.”
“We are excited by this early data for HPN424 and the broader application of our technology. Our novel TriTAC drug candidates are designed to enable a patient’s own T cells to fight tumors in a wide range of human malignancies,” said Jerry McMahon, Ph.D., President and Chief Executive Officer of Harpoon. “We are looking forward to reporting additional clinical data from our ongoing HPN424 Phase 1 clinical trial in 2019 as we continue to enroll and analyze data from existing and new patients.”
Phase 1 Trial Observations (As of December 31, 2018)
Patient Treatment and Tolerability: Seven patients have been treated in the dose escalation portion of the trial, at doses ranging from 1.3 to 24 ng/kg. All seven have been treated previously with a second-generation anti-androgen therapy. All seven patients remain on study treatment, with the time on treatment ranging from one to more than twenty weeks, and the number of doses received ranging from one to 22 weekly treatments. No dose limiting toxicities have been observed. One patient experienced a grade 3 CRS event which resolved within eight hours of dosing. This patient was re-administered HPN424 consistent with protocol guidelines. The patient experienced no further reactions and continues to be enrolled in the study. Based on this event, the dose escalation is proceeding using three to six patients per cohort consistent with the original Phase 1 plan.
Serum Drug Exposure: Preliminary pharmacokinetic analysis supports at least once weekly dosing. Maximum serum concentration of HPN424 was found to be proportional to the dose. The volume of distribution and clearance rates appear to be similar among different dose levels suggesting linear pharmacokinetic properties.
T Cell Engagement: Transient and dose-dependent increases in peripheral cytokines (interleukin-6, interleukin-8, interleukin-10) and chemokines (macrophage inflammatory protein-1-alpha, macrophage inflammatory protein-1-beta, monocyte chemoattractant protein-1) were observed, consistent with the expected mechanism of action related to T cell activation.
Tumor Assessments: Radiographic assessment of disease burden is performed at nine-week intervals. For the first three patients in the trial, radiographic and PSA data have shown stable disease for two patients and one patient exhibited unconfirmed progressive disease. The other four patients are early in their treatment and not yet evaluable. Whole blood samples from three of four patients with measurable baseline CTC levels showed a reduction in CTC following treatment with HPN424.
About HPN424-1001 Clinical Trial
The HPN424-1001 Phase 1 trial is a multicenter, open-label dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and activity of HPN424, a novel T cell engaging therapeutic that targets PSMA (clinicaltrials.gov ID#: NCT03577028). Eligible patients must have mCRPC, have received at least two prior regimens for mCRPC, and have evidence of disease progression on the most recent systemic regimen. In the first part of the trial, HPN424 is administered once weekly via intravenous infusion in ascending dose cohorts until a therapeutic dose is achieved. Following dose escalation, the study will expand and enroll approximately twenty patients at the recommended Phase 2 dose established in the first part of the trial.
About Harpoon Therapeutics
Harpoon Therapeutics is a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases. T cell engagers are engineered proteins that direct a patient’s own T cells to kill target cells that express specific proteins, or antigens, carried by the target cells. Using its proprietary Tri-specific T cell Activating Construct™ (TriTAC), platform, Harpoon is developing a pipeline of novel T cell engagers, or TriTACs, initially focused on the treatment of solid tumors and hematologic malignancies. Harpoon recently announced its second technology platform, ProTriTAC, that applies a prodrug concept to TriTAC in order to create T cell engagers that are designed to be preferentially active in the tumor microenvironment.
