HPN424 Shows Promising Safety, Immune Activation in Metastatic CRPC

HPN424 Shows Promising Safety, Immune Activation in Metastatic CRPC
Preliminary data from an ongoing Phase 1 trial suggest that Harpoon Therapeutics’ investigational therapy HPN424 is safe and effectively activates the immune system in metastatic castration resistant prostate cancer (mCRPC) patients. The multicenter, international, open-label study (NCT03577028) is assessing the safety, tolerability and overall stability and distribution of HPN424 in about 40 adult patients with mCRPC. “These initial results in advanced mCRPC patients suggest that HPN424 is activating T cells in a manner that is consistent with tumor target engagement,” Natalie Sacks, MD, chief medical officer of Harpoon, said in a press release. HPN424, built with Harpoon’s TriTAC (Tri-specific T cell Activating Construct) technology, is meant to work as a connector between tumor cells and the patient's own T cells. In particular, it binds the validated target PSMA protein — found in more than 90 percent of mCRPC lesions — and the CD3 molecule on T cells. Harpoon designed HPN-424 to be the smallest T-cell engager to penetrate solid tumors with superior effectiveness, last longer in the blood, and recruit patients’ T cells to kill cancer cells. “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,” said Holger Wesche, PhD, chief scientific officer of Harpoon. To date, seven patients have been included in Harpoon's Phase 1/2 trial, all of whom had received prior treatment with a second-generation anti-androgen therapy, such as Zytiga (abiraterone) and Xtandi (enzalutamide). They received ascending doses of HPN424 — ranging from 1.3 to 24 nanograms per kg — w
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