Single-center phase 2 study of the MEK1/2 inhibitor luvometinib in patients with extracranial arteriovenous malformations

Extracranial arteriovenous malformation (AVM) is a rare and debilitating condition with significant morbidity. A phase 2 study at Shanghai Jiao Tong University School of Medicine (Shanghai, China) evaluated the MEK1/2 inhibitor luvometinib in adults with AVMs that were inoperable, unsuitable for intervention, relapsed after surgery, or failed previous treatment. Patients received luvometinib 8 mg once daily in 28-day cycles. Primary endpoint was objective response rate (ORR; patients with ≥ 20% reduction in lesion range) by digital subtraction angiography (DSA). Among 20 patients enrolled, 18 had stage III AVM. The median duration of follow-up was 14.6 months. ORR by DSA was 64.3% (95% CI 35.1-87.2), with major partial response (lesion reduction > 50%) in 35.7%. ORR by MRI was 61.1% (95% CI 35.7-82.7). Fourteen (77.8%) and 15 (83.3%) patients had improvements iin arterial velocity and impedance, respectively. Response was achieved in RAS-MARK-mutated, EPHB4-mutated, or mutation-undetected patients, but not in RASA1-mutated patients. Nineteen patients (95%) experienced treatment-related adverse events; mostly grade 1 or 2; 5 patients had grade 3 or 4 TRAEs. No grade 5 TRAEs were observed. The authors conclude that luvometinib demonstrated promising efficacy and tolerability, supporting its further development for treatment of AVMs.