Efficacy and safety of regorafenib in patients with advanced pretreated melanoma: results of the RegoMel phase II clinical trial

BACKGROUND: Most patients with advanced melanoma progress despite standard-of-care treatments. Regorafenib (REGO), an oral multikinase inhibitor with RAF-dimer activity, demonstrated clinical activity in melanoma in retrospective case series and preclinical efficacy in overcoming resistance to BRAF/MEK inhibitors (BRAF/MEKi). This study prospectively evaluated REGO in heavily pretreated advanced melanoma patients. PATIENTS AND METHODS: -mutant patients, BRAF/MEKi addition was permitted upon progression on REGO monotherapy. Based on early efficacy signs, a KIT-mutant expansion cohort was also recruited and analyzed. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: -mutant patients received REGO + BRAF/MEKi at first progression (ORR 33%, DCR 83%, mPFS 20.4 weeks, mOS 62.1 weeks). Grade 3 treatment-related adverse events (TRAEs) occurred in 59% of patients on REGO monotherapy and 50% on REGO + BRAF/MEKi. The most common TRAEs were hand-foot-skin reaction, hypertension, and diarrhea. All TRAEs were reversible. CONCLUSION: -mutant patients receiving REGO + BRAF/MEKi support further investigation of REGO-based regimens in these subpopulations of melanoma patients.