First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations.

ABSTRACT:

Background

HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.

Methods

This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.

Results

Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 

SUBMITTER: Wang X 

PROVIDER: S-EPMC9814429 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature