Phase I data regarding the experimental cancer agent ONT-380 were presented recently at the 2015 San Antonio Breast Cancer Symposium (8–12 December, TX, USA), indicating initial efficacy in breast cancer patients with metastatic HER2+ breast cancer. The agent was noted to be particularly effective against brain metastases and the data overall from NCT01983501 were suggested to support the commencement of a Phase II investigation.
The results presented demonstrated that of 33 evaluable patients, 19 (or 58 %) derived some clinical benefit from the treatment, with 16 of these individuals achieving at least stable disease. Eleven of these patients experienced a partial response and of the eight patients with brain metastases, five achieved at least stable disease, with 2 partial responses and one complete response in which existing brain metastases were undetectable after treatment.
Specifically, ONT-380 is a small molecule HER2-receptor inhibitor. The fact that this agent is a small molecule in form enables it to pass through the blood–brain barrier, facilitating its action on brain tumors. Side effects of ONT-380 as recorded in the trial were mild and commonly included nausea, fatigue, diarrhea, vomiting, thrombocytopenia, AST/ALT elevation, headache, decreased appetite, epistaxis, constipation and hypokalemia.
“When you look at the clinical benefit for women previously treated, we’ve had patients with controlled brain lesions for over 6 months or a year, which is pretty unheard of,” commented Virginia Borges of the University of Colorado Cancer Center (CO, USA), one of the study’s coprincipal investigators. “And they’re able to get this benefit by taking a pill that has essentially no side effects for most women.”
“I don’t want to downplay this drug’s potential to provide overall control of HER2+ breast cancer, but it’s a real game-changer for its specific ability to control brain metastases. What distinguishes ONT-380 from other players in the field is that you get both,” Borges continued. “If ONT-380 continues its current trajectory, we hope it could present a real option for controlling brain metastases in HER2+ breast cancer.”