Phase 2a trial of tunlametinib in adults with inoperable neurofibromatosis type 1-associated plexiform neurofibromas

Tunlametinib is an orally active MEK1/2 inhibitor. A phase 2a trial at Shanghai Ninth People’s Hospital (China) evaluated tunlametinib at a dose of 9 mg twice daily, following a continuous 21-day cycle regimen in 15 adult patients (10 males and 5 females; median age 27 years, range 18-45) with inoperable, radiologically measurable plexiform neurofibromas (PN). The primary endpoint was confirmed objective response rate (ORR). Eight patients achieve a confirmed partial response (ORR 53.3%; 95% CI 26.7-78.7) with a median neurofibroma volume reduction of -23.5% (range 1.6 to -49.1). Significant improvements in multiple patient-reported outcome domains were observed. All patients experienced at least on-treatment related adverse event, the majority of which were grade 1 or 2. The authors conclude that tunlametinib demonstrated promising efficacy and an acceptable safety profile in adults with PN.