Efficacy results of a phase 1b study of ONT 380, a CNS penetrant TKI, in combination with T DM1 in HER2+ metastatic breast cancer (MBC) including patients (pts) with brain metastases.
513Background: Modern registry data of MBC (Hurvitz '15; Witzel '15) suggest that HER2+ pts with CNS metastases (CNS+ have a poor prognosis. CNS disease is also associated with worse PS QOL scores. Most systemic treatments for MBC have limited brain penetration clinical trials often exclude CNS+ pts, causing a lack of prospective data on the outcome of CNS+ pts treated (tx) in the post pertuzumab (P) T DM1 era. We report here the efficacy results of CNS+ CNS pts tx at the RP2D of TDM1 ONT 380, a HER2 selective TKI with CNS penetration. Methods: Study ONT 380 004, a Phase 1b study of T DM1 escalating doses of ONT 380, enrolled HER2+ MBC pts, including pts with previously tx CNS lesions (stable or progressive) or untreated asymptomatic CNS lesions. We report the efficacy results in all pts tx at the RP2D of ONT 380 (300 mg BID) TDM1 (3.6 mg/kg IV q 21 days) tx before 6/15/15. Eligibility: HER2+ MBC post taxane/trastuzumab (T) RECIST 1.1 measurable or non measurable disease. All pts had base.