Vabametkib, a selective oral c-MET inhibitor, has shown anti-tumor activity in preclinical studies, both as monotherapy and in combination with other treatments. ASCO 2025 has brought its Phase II study results for patients with MET exon 14 skipping NSCLC. As of December 24, 2024, the study demonstrated an Objective Response Rate (ORR) to be 43.2%, with 16 out of 37 patients achieving a response. The median Progression-free Survival (PFS) was 15.9 months for treatment-naive patients and 6.2 months for previously treated patients. The median follow-up for the efficacy population was 7.7 months. 

Vabametkib’s safety was assessed in all 40 treated patients, the most common treatment-related adverse events were nausea, diarrhea, and vomiting, and peripheral edema. Grade 3 or higher adverse events occurred in 5 patients, no Grade 3 edema were reported in the study population. No Grade 5 events in this cohort.

KOL insights

“ABN401 is a potent and highly selective MET inhibitor in MET-addicted cancers and shows a favorable PK profile. The testing of ABN401 in clinical trials may be improved by establishing guidelines for patient selection and determining the effective dosage and treatment durations of ABN401 required to inhibit c-MET activity.” – Expert Opinion.

Conclusion

As per the DelveInsight estimates, the total market size of c-MET NSCLC was around USD 2 billion in 2024. METex14, present in nearly 3–4% of NSCLC cases, are now recognized as key targets due to their association with poor prognosis and limited response to standard therapies. Globally approved MET TKIs such as TABRECTA, TEPMETKO, EMRELIS, HAIYITAN, and ORPATHYS (China) are standard treatments. In addition to approved therapies, promising emerging treatments include the combination of Savolitinib and TAGRISSO, MCLA-129, Vebreltinib, and others.

In this competitive scenario, vabametkib demonstrated good antitumor activity in patients with METex14 NSCLC, and better toxicity profile with excellent tolerability, compared to FDA approved MET inhibitors, supporting vabametkib continued clinical development for METex14 NSCLC patients.