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only). Patients will receive tucatinib 300 mg orally twice a day and trastuzumab 8 mg/ kg intravenously on Cycle 1 Day 1 then 6 mg/kg every 21 days from Cycle 2 Day 1. Disease assessments per RECIST 1.1 are every 6 weeks for the first 24 weeks, then every 12 weeks. Quality of life will be evaluated every 2 cycles using EQ-5D-5L. Enrollment at US sites began in December 2020, and site initiation is in progress in Asia and the EU.Clinical trial identification: NCT04579380.