First Patient Dosed on ONT-380 HER2-Positive Breast Cancer Trial

The dual action of ONT-380, which is an oral, HER2-selective, central nervous system (CNS)-active tyrosine kinase inhibitor, may be able to help women combat advanced HER2-positive breast cancer.  

On February 29, 2016, the company developing this compound, Oncothyreon Inc., announced the dosing of the first patient in a randomized, placebo-controlled, phase II trial of ONT-380 in combination with Herceptin (trastuzumab) and Xeloda (capecitabine).

ONT-380 selectively inhibits HER2 without significant inhibition of EGFR, which is also called HER1. This agent, based on its design, may help prevent side effects associated with dual inhibitors, including skin rash and gastrointestinal toxicities. In addition, ONT-380 has been shown to have durable, objective responses in HER2-positive patients with brain metastases.

The trial is currently enrolling patients at Providence Cancer Center in Portland, Ore., and at Sarah Cannon Research Institute in Nashville, Tenn. This international, multicenter study is looking to enroll approximately 180 patients in the United States, much of Canada, as well as countries in Western Europe. The trial will include those patients with HER2-positive breast cancer that have been previously treated with a taxane, trastuzumab, Perjeta (pertuzumab), and Kadcyla (ado-trastuzumab emtansine or T-DM1)with or without brain metastases.

"There is a great need for effective, well-tolerated treatments for women with progressing metastatic HER2-positive breast cancer, especially those with metastases to the brain, which develops in up to half of these patients and who are frequently excluded from clinical trials. With no approved therapy for the treatment of brain metastases, options for this patient population are currently limited," said study investigator Erika Hamilton, MD, director, Breast and Gynecologic Cancer Research Program, Sarah Cannon Research Institute, in a news release.

Dr. Hamilton said this trial includes specifically designed endpoints around HER2-positive CNS disease to further explore the activity of ONT-380 in combination with trastuzumab and capecitabine on brain metastases. The trial will explore how effective ONT-380 is in the third-line metastatic setting and assess the efficacy, safety, and pharmacokinetics of ONT-380 in combination with trastuzumab and capecitabine. The primary endpoint is progression-free survival (PFS) based on assessment of both CNS and non-CNS disease. Additional endpoints include time to CNS progression, objective response rate (ORR), and overall survival (OS).