Related Experiment Video
Updated: May 14, 2026
A Patient-Derived Xenograft Model for Venous Malformation
Published on: June 15, 2020
A Phase 2 Study of the MEK1/2 Inhibitor Luvometinib in Patients with Extracranial Arteriovenous Malformations
Chen Hua1, Zhuli Wu2, Xingli Wang2
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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 magnetic resonance imaging (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% confidence interval (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 to 2; 5 (25%) had grade ≥3. No deaths were 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.
Insights
Luvometinib shows promise in treating complex extracranial arteriovenous malformations (AVMs) in adults. This targeted therapy demonstrated significant lesion reduction and symptom improvement with manageable side effects.
Area of Science:
- Vascular Surgery
- Medical Oncology
- Pharmacology
Background:
- Extracranial arteriovenous malformation (AVM) is a rare, debilitating vascular disorder with limited targeted therapy options.
- Existing treatments for complex AVMs often involve invasive procedures with significant risks and suboptimal outcomes.
- The MEK1/2 pathway is implicated in vascular malformations, making it a potential therapeutic target.
Purpose of the Study:
- To evaluate the efficacy and safety of luvometinib, a MEK1/2 inhibitor, as a targeted therapy for adults with complicated, inoperable, or relapsed extracranial AVMs.
- To assess the objective response rate (ORR) of luvometinib based on lesion size reduction via digital subtraction angiography (DSA) and MRI.
- To investigate secondary endpoints including lesion clearance, hemodynamic improvements, clinical symptom resolution, and treatment tolerability.
Main Methods:
- A single-arm, phase 2 clinical trial was conducted, enrolling 20 adult patients with inoperable or relapsed extracranial AVMs.
- Patients received oral luvometinib 8 mg once daily in 28-day cycles.
- Primary efficacy endpoint was ORR defined as ≥20% reduction in lesion range on DSA; secondary endpoints included MRI-based ORR, hemodynamic parameters, clinical symptoms, and safety assessments.
Main Results:
- The objective response rate (ORR) by DSA was 64.3%, with 35.7% achieving major partial response (lesion reduction >50%).
- MRI-based ORR was 61.1%. Significant improvements in arterial velocity (77.8%) and impedance (83.3%) were observed.
- Luvometinib was generally well-tolerated, with most treatment-emergent adverse events being grade 1-2. Response was noted across various mutation profiles, excluding RASA1-mutated patients.
Conclusions:
- Luvometinib demonstrated promising efficacy in reducing lesion size and improving clinical symptoms in adults with inoperable or relapsed extracranial AVMs.
- The targeted therapy exhibited a favorable safety profile, with manageable adverse events.
- These findings support the further development of luvometinib as a potential targeted treatment for complex extracranial AVMs.
