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[Business Wire] Harpoon Announces Preliminary Safety and PharmacologyData from its HPN424 Phase 1 Trial in Prostate Cancer

Juhee Kim Juhee Kim
2019-01-25 19:23
원본기사주소↓ (Jan 2th, 2019)

Harpoon Therapeutics, Inc. ("Harpoon"), a clinical-stage immunotherapycompany developing a novel class of T cell engagers that harness thepower of the body's immune system to treat patients with cancer andother diseases, today announced preliminary safety and mechanism ofaction findings from an ongoing Phase 1 clinical trial evaluating itslead compound, HPN424, in patients with progressive metastaticcastration resistant prostate cancer (mCRPC). The Phase 1 trial is amulticenter, open-label dose escalation and dose expansion study toevaluate the safety, tolerability, pharmacokinetics and clinicalactivity of HPN424, a TriTAC (Tri-specific T Cell Activating Construct)that targets prostate-specific membrane antigen (PSMA), a clinicallyvalidated tumor antigen target in prostate cancer.

Eligible patients must have mCRPC, have received at least two priortreatment regimens for mCRPC, and have evidence of disease progressionon the most recent systemic treatment regimen. Clinical observationsfrom the first seven prostate cancer patients treated with HPN424include:

* Measurement of drug in the sera from patients indicates sufficientdrug exposure during the treatment course to support once weeklydosing.

* Measurable reduction in circulating tumor cells (CTC) in three of fourpatients evaluated as a biomarker for PSMA target engagement.

* Dose-dependent, transient increase in peripheral cytokine andchemokine levels, consistent with the expected T cell activationmechanism of action.

* No dose limiting toxicities have been observed to date, with four doselevels tested.

* Adverse events were consistent with the expected mechanism of action,with three patients reporting grade 2 rigors or fevers that weremanageable. A grade 3 cytokine release syndrome (CRS) event wasreported in one patient from the fourth cohort but resolved withineight hours. All patients experiencing adverse events weresuccessfully 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 computedtomography scans, bone scans and measurement of prostate serum antigenlevels. To date, two patients have shown stable disease and onepatient exhibited unconfirmed progressive disease and continues onstudy. The other four patients are early in their treatment and havenot yet been evaluated for disease burden.

“These initial results in advanced metastatic castration resistantprostate cancer patients suggest that HPN424 is activating T cells in amanner that is consistent with tumor target engagement,” said NatalieSacks, M.D., Chief Medical Officer of Harpoon. Dr. Sacks added, “We haveobserved early signals confirming the mechanism of action of HPN424, andhave obtained encouraging safety data that supports continued doseescalation to define a Phase 2 therapeutic dose and regimen.”

“These results provide the first clinical evidence suggesting Harpoon’sTriTAC platform is performing as designed, by activating T cells in atarget-dependent manner and by showing evidence of sufficient drugexposure during the treatment course to support once weekly dosing,” said Holger Wesche, Ph.D., Chief Scientific Officer of Harpoon. “HPN424is a novel T cell biologic that has been designed to deliver potent Tcell killing to PSMA-expressing tumor cells. We are encouraged by theearly human safety and pharmacology data emerging from our Phase 1trial.”

“We are excited by this early data for HPN424 and the broaderapplication of our technology. Our novel TriTAC drug candidates aredesigned to enable a patient’s own T cells to fight tumors in a widerange of human malignancies,” said Jerry McMahon, Ph.D., President andChief Executive Officer of Harpoon. “We are looking forward to reportingadditional clinical data from our ongoing HPN424 Phase 1 clinical trialin 2019 as we continue to enroll and analyze data from existing and newpatients.”

[Phase 1 Trial Observations (As of December 31, 2018)]

* Patient Treatment and Tolerability: Seven patients havebeen treated in the dose escalation portion of the trial, at dosesranging from 1.3 to 24 ng/kg. All seven have been treated previouslywith a second-generation anti-androgen therapy. All seven patientsremain on study treatment, with the time on treatment ranging from oneto more than 20 weeks, and the number of doses received ranging from oneto 22 weekly treatments. No dose limiting toxicities have been observed.One patient experienced a grade 3 CRS event which resolved within eighthours of dosing. This patient was re-administered HPN424 consistent withprotocol guidelines. The patient experienced no further reactions andcontinues to be enrolled in the study. Based on this event, the doseescalation is proceeding using three to six patients per cohortconsistent with the original Phase 1 plan.

* Serum Drug Exposure: Preliminary pharmacokinetic analysissupports at least once weekly dosing. Maximum serum concentration ofHPN424 was found to be proportional to the dose. The volume ofdistribution and clearance rates appear to be similar among differentdose levels suggesting linear pharmacokinetic properties.

* T Cell Engagement: Transient and dose-dependent increasesin peripheral cytokines (interleukin-6, interleukin-8, interleukin-10)and chemokines (macrophage inflammatory protein-1-alpha, macrophageinflammatory protein-1-beta, monocyte chemoattractant protein-1) wereobserved, consistent with the expected mechanism of action related to Tcell activation.

* Tumor Assessments: Radiographic assessment of diseaseburden is performed at nine-week intervals. For the first three patientsin the trial, radiographic and PSA data have shown stable disease fortwo patients and one patient exhibited unconfirmed progressive disease.The other four patients are early in their treatment and not yetevaluable. Whole blood samples from three of four patients withmeasurable baseline CTC levels showed a reduction in CTC followingtreatment with HPN424.

[About HPN424-1001 Clinical Trial]

* The HPN424-1001 Phase 1 trial is a multicenter, open-label doseescalation and dose expansion study to evaluate the safety,tolerability, pharmacokinetics and activity of HPN424, a novel T cellengaging therapeutic that targets PSMA (clinicaltrials.gov ID#:NCT03577028). Eligible patients must have mCRPC, have received at leasttwo prior regimens for mCRPC, and have evidence of disease progressionon the most recent systemic regimen. In the first part of the trial,HPN424 is administered once weekly via intravenous infusion in ascendingdose cohorts until a therapeutic dose is achieved. Following doseescalation, the study will expand and enroll approximately 20 patientsat the recommended Phase 2 dose established in the first part of thetrial.

[About Harpoon Therapeutics]

* Harpoon Therapeutics is a clinical-stage immunotherapy companydeveloping a novel class of T cell engagers that harness the power ofthe body’s immune system to treat patients suffering from cancer andother diseases. T cell engagers are engineered proteins that direct apatient’s own T cells to kill target cells that express specificproteins, or antigens, carried by the target cells. Using itsproprietary Tri-specific T cell Activating Construct™ (TriTAC),platform, Harpoon is developing a pipeline of novel T cell engagers, orTriTACs, initially focused on the treatment of solid tumors andhematologic malignancies. Harpoon recently announced its secondtechnology platform, ProTriTAC, that applies a prodrug concept to TriTACin order to create T cell engagers that are designed to bepreferentially active in the tumor microenvironment.