Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.

This study is a multicenter, single arm, open-label, run-in phase Ib safety cohort with immediate roll over to a phase II clinical trial that will test the combination therapy of tucatinib with alpelisib in subjects with PIK3CA-mutant HER2+ locally advanced unresectable or metastatic breast cancer. Patients with PIK3CA-mutant HR-/HER2+ and HR+/HER2+ breast cancer may enroll, the latter cohort will receive concomitant treatment with standard doses of fulvestrant to block HR signaling. In phase Ib part, we will confirm the tolerability of tucatinib and alpelisib combination and determine the maximum tolerated dose (MTD). In phase II part, we will expand the testing of this drug combination at MTD to determine the PFS rate.