Erika Hamilton of Sarah Cannon Research Institute, Nashville, TN talks about a Phase I trial of ONT-380 in combination with capecitabine and T-DM1 (trastuzumab emtansine), in patients with HER2+ metastatic breast cancer (NCT02025192). ONT-380 is a potent small molecule selective inhibitor of HER2. She explains that what is exciting about this compound is that it also crosses into the brain; as a result, what was unusual is that patients with both untreated and treated brain metastases were also allowed into the study, making the patients a very high risk population. The study showed that the response rate of ONT-380 in combination with T-DM1 was 47%, with a progression-free survival (PFS) of over 8 months. The actual central nervous system (CNS) activity showed that over a third of patients responded in the brain, showing very promising results for this study. Recorded at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago, IL.