Harpoon Therapeutics announced the first patient has been dosed with HPN328, a delta like ligand 3- (DLL3) targeting TriTAC?, in a Phase 1/2 clinical trial as an investigational treatment of small cell lung cancer (SCLC) and other tumors associated with DLL3 expression. The company has presented preclinical data on HPN328 showing that the drug was well tolerated in cynomolgus monkeys at 1 and 10 mg/kg, and pharmacokinetic data supported the potential for once weekly dosing. When administered to mice bearing human SCLC xenografts and human T cells, HPN328 eradicated tumors.

“We are pleased with the rapid progress of our clinical programs, based on our proprietary TriTAC platform, with patient dosing now underway for our fourth product candidate, HPN328, that targets DLL3,” said Natalie Sacks, M.D., Chief Medical Officer of Harpoon Therapeutics. “Treatment options for small cell lung cancer are limited, as are options for other DLL3-associated tumors such as neuroendocrine prostate cancer. Data from preclinical studies suggest that HPN328 has substantial anti-tumor activity, which provides the rationale for investigating its potential benefit in these patients.”

“We are excited to participate in this trial of a promising agent that will hopefully benefit patients with small cell lung cancer and other neuroendocrine tumors,” said Melissa Johnson, M.D., Program Director of Lung Cancer Research at Sarah Cannon Research Institute. The first patient was treated at Sarah Cannon Research Institute at Tennessee Oncology.

“I am excited that Harpoon’s fourth TriTAC drug candidate, HPN328, has advanced into the clinic focusing on SCLC, an aggressive and deadly disease with a significant unmet need, as its initial indication,” said Jerry McMahon, Ph.D., President and Chief Executive Officer of Harpoon Therapeutics. “Each of Harpoon’s four TriTAC clinical programs are progressing well and we expect data to emerge from our clinical trials throughout 2021.”

HPN328 is a TriTAC that binds to human and non-human primate DLL3, CD3ε, and albumin with similar affinities. The Phase 1/2 trial is an open-label study of HPN328 as monotherapy to assess the safety, tolerability and pharmacokinetics in patients with advanced cancers associated with expression of DLL3. The first part of the trial is designed to determine a dose for additional clinical investigations. The trial plans to enroll patients with SCLC that have relapsed following at least one line of platinum-based chemotherapy. HPN328 will be administered to patients once weekly by intravenous infusion with dose escalation until a therapeutic dose level has been achieved. The primary outcome measure will be to assess safety and tolerability, and to determine a dose for Phase 2.

Following dose escalation, Harpoon may further evaluate the safety and efficacy of HPN328 in additional parallel cohorts. The primary outcome measure will be to determine efficacy for the Phase 2 dose based on the overall response rate as determined by RECIST.