Trastuzumab emtansine (T-DM1) plus capecitabine (X) in patients with HER2-positive MBC: MO28230 TRAX-HER2 phase 1 results.

606 Background: T-DM1, an antibody–drug conjugate composed of trastuzumab, the microtubule inhibitor DM1, and a stable linker, is a newly approved therapy for HER2-positive MBC. Two phase 3 studies have shown significant efficacy in patients previously treated with trastuzumab and a taxane. HER2-directed therapies in combination with X have shown improved efficacy in patients with MBC, and preclinical data show enhanced activity with T-DM1 + 5-fluorouracil. Thus, T-DM1 + X may have increased antitumor activity in patients with HER2-positive MBC. Methods: TRAX-HER2 (NCT01702558) is a phase 1/2 study of T-DM1 + X in patients with HER2-positive MBC (IHC 3+/ISH+) or metastatic gastric cancer. Key inclusion criteria are progression on ≥1 trastuzumab + chemotherapy regimen, ≥1 measurable lesion (RECIST v1.1), and LVEF ≥50%. The primary phase 1 objective for MBC was to evaluate the maximum tolerated dose (MTD) of X with T-DM1 (3.6 mg/kg q3w) using a 3 + 3 design. Safety, tumor response, and PK were also assessed...