A Phase Ib Trial Of Copanlisib And Tratuzumab In Pretreated Recurrent Or Metastatic Her2-Positive Breast Cancer "Panther"

1036Background: PI3K pathway activation is implicated in resistance to trastuzumab (T) therapy in breast cancer (BC). Copanlisib (C) is a pan-class I PI3K inhibitor with particular activity against PI3Kα, the isoform encoded by the PIK3CA gene. PIK3CA mutation may predict response to PI3K inhibition. Methods: The maximum tolerated dose (MTD) and safety of C + T were evaluated in an open label, single arm, adaptive multicenter phase Ib dose escalation clinical trial in patients (pts) with HER-2 positive BC. Eligible pts had disease progression following at least one line of (T) or TDM-1 based therapy in the metastatic setting. Pts were treated with T (4mg/kg loading dose then 2mg/kg weekly) given with C intravenously on Day 1, 8 + 15 of 28 day cycle at one of two dose levels (DL) according to a modified 3+3 (6+6) design. Cycle 1 safety data were used to determine dose limiting toxicities (DLTs). Disease assessments were made every 8 weeks. PIK3CA mutation status was determined in formalin-fixed paraffin-em...