Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer.

ABSTRACT:

Background

Dual inhibition of PI3K and MAPK signaling is conceptually a promising anticancer therapy.

Objective

This phase 1b trial investigated the safety, maximum tolerated dose (MTD), recommended phase II dose, pharmacokinetics, tumor response, fluorodeoxyglucose positron emission tomography (FDG-PET) pharmacodynamics, and biomarker explorations for the combination of pan-PI3K inhibitor copanlisib and allosteric MEK inhibitor refametinib in patients with advanced solid tumors.

Patients and methods

This was an adaptive trial with eight dose cohorts combining dose escalation and varying schedules in repeated 28-day cycles. Patients received copanlisib (0.2-0.8 mg/kg intravenously) intermittently (days 1, 8, 15) or weekly (days 1, 8, 15, 22) each cycle, and refametini

SUBMITTER: Ramanathan RK 

PROVIDER: S-EPMC7591420 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature