Part 1: Dose confirmation:~Primary Objective:~• To evaluate the safety, tolerability, and dose-limiting toxicities (DLT) of copanlisib 60 mg administered intravenously (IV) on Days 1, 8 and 15 in combination with fulvestrant 500 mg administered intramuscularly (IM) on Day 1 and Day 15 of Cycle 1, and then on Day 1 of each subsequent 28-day cycle to confirm the recommended phase 2 doses (RP2D) of the combination therapy.~Secondary objective:~To assess the efficacy of copanlisib administered in combination with fulvestrant as outlined in Part 2 by evaluating the objective response rate (ORR).~To evaluate additional efficacy measures such as progression-free survival (PFS) and overall survival (OS) of copanlisib in combination with fulvestrant.~Exploratory Objectives:~To investigate target engagement, clonal evolution, and mechanisms of resistance using tissue and liquid biopsies utilizing circulating tumor DNA (ctDNA) as outlined in Part 2.~To characterize the pharmacokinetics (PK) of copanlisib and fulvestrant when given in combination.~Part 2: Dose expansion:~Primary objectives:~• To assess the efficacy of copanlisib administered in combination with fulvestrant as outlined above by evaluating the objective response rate (ORR). Patients enrolled for Part 1 will be included in this efficacy analysis.~Secondary Objectives:~To evaluate additional efficacy measures such as PFS and OS of copanlisib in combination with fulvestrant.~To evaluate the safety and tolerability of copanlisib in combination with fulvestrant.~Exploratory Objectives:~To investigate target engagement, clonal evolution, and mechanisms of resistance using tissue and liquid biopsies utilizing ctDNA.~To characterize the PK of copanlisib and fulvestrant when given in combination.
The purpose of this study is to evaluate the efficacy and safety of copanlisib in combination with fulvestrant in advanced hormone receptor-positive (HR+) solid tumors harboring alterations that activate the Phosphatidylinositol-3 kinase (PI3K) pathway.