Tucatinib, Palbociclib and Letrozole in Metastatic Hormone Receptor Positive and HER2-positive Breast Cancer

This is a multicenter, single arm, open-label, run-in phase Ib / roll-over phase II study of novel HER2-targeted tyrosine kinase inhibitor tucatinib in combination with CDK4/6 inhibitor palbociclib and aromatase inhibitor letrozole in subjects with HR+/HER2+ locally advanced unresectable or metastatic breast cancer. The study will enroll post-menopausal women and premenopausal women if on treatment with or willing to be treated with standard ovarian suppression. The phase Ib part of the study will determine safety and tolerability of the combination of tucatinib, palbociclib and letrozole to confirm that current RP2D of tucatinib and FDA approved dosing of palbociclib remains the same in the triplet combination. The dose of letrozole will be constant through the study period. Once the safety of the combination is established, we will move to the phase II part of the study in the expansion cohort of subjects at RP2D for the purpose of assessing efficacy while further refining assessment of safety of the combination treatment.