PURPOSE: Extracranial arteriovenous malformation (AVM) is a rare and debilitating condition with significant morbidity. Clinical trial evidence for targeted therapies remains limited. We evaluated the efficacy and safety of luvometinib, a MEK1/2 inhibitor, in adults with complicated AVM that were inoperable, unsuitable for intervention, relapsed after surgery, or failed previous treatment. PATIENTS AND METHODS: This single-arm phase 2 study enrolled adults with inoperable or relapsed extracranial AVMs. 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). Secondary endpoints included ORR (patients with ≥20% reduction in volume) by MRI, lesion clearance, improvement in arterial flow and impedance, clinical symptoms, and safety. RESULTS: We enrolled 20 patients; 18 (90%) had stage III AVM (median follow-up duration 14·6 months). ORR by DSA was 64·3% (lesion reduction ≥20%; 95% CI 35·1-87·2); 35·7% achieved major partial response (lesion reduction >50%). ORR by MRI was 61·1% (95% CI 35·7-82·7). Fourteen (77·8%) and 15 (83·3%) patients had improvements in arterial velocity and impedance, respectively; 12 (66·7%) had improvements in clinical symptoms. Response was achieved in RAS-MARK-mutated, EPHB4-mutated, or mutation-undetected patients, but not RASA1-mutated patients. Nineteen (95%) patients experienced treatment-emergent adverse events, mostly grade 1-2; 5 (25%) had grade ≥3. No deaths reported. CONCLUSIONS: In the first clinical trial of targeted therapy in adults with inoperable or relapsed extracranial AVMs, luvometinib demonstrated promising efficacy and tolerability, supporting its further development for the treatment of AVMs.
Hua et al. (2026) studied this question.