NSABP FB-10: Phase Ib dose-escalation trial evaluating trastuzumab emtansine (T-DM1) with neratinib (N) in women with metastatic HER2+ breast cancer (MBC).

1027Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab and the maytansinoid antimicrotubule, DM1. T-DM1 was granted FDA approval in 2nd-line MBC after prior trastuzumab (T) and taxane. Current practice in USA is for pts to receive T and pertuzumab (P) as neoadjuvant or as 1st-line therapy. Retrospective analysis of T-DM1 after T-P suggests a lower response rate (17%) than T-DM1 after T and taxane (EMILIA 43%). This study investigates the safety and efficacy of T-DM1 + N. Methods: Eligible pts had prior T-P as neoadjuvant therapy or in 1st-line, measurable disease, ECOG PS ≤2, adequate hematologic, renal, and liver function. Pts with stable brain metastases (CNS) were eligible. Treatment was T-DM1 at 3.6 mg/kg iv q 3 wk and N at escalating doses of 120, 160, 200, and 240 mg/d using 3+3 design. HER2 + was required on primary tissue but was not reassessed at entry. Blood samples were required upon entry. Pharmacokinetic (PK) studies were performed on a limited number of pts. Primary diar...