Vabametkib in MET exon 14 skipping non-small-cell lung cancer: Efficacy and safety from the open-label, phase 2, cohort-1 trial

초록

Background: Vabametkib (ABN401) is a tyrosine kinase inhibitor (TKI) targeting MET. It has previously demonstrated preliminary efficacy in patients(pts) with MET genomic aberrations including MET exon 14 skipping mutation (METex14) in lung cancer. Here, we present the efficacy and safety data from cohort 1 (TKI-naïve, METex14 non-small cell lung cancer [NSCLC]) Methods: Phase 2 Cohort 1 trial (NCT05541822) is an open-label, global, multicenter study designed to evaluate the safety and efficacy of vabametkib in pts with NSCLC harboring METex14. METex14 status is confirmed via NGS testing and the status is further validated centrally using digital droplet PCR (ddPCR). Pts receive oral vabametkib at a dose of 800 mg once daily (QD) until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is the objective response rate (ORR). Additional outcomes being evaluated include pharmacokinetics (PK), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: This study was conducted across 24 centers in three countries (US, South Korea, and Taiwan). A total of 40 pts with METex14 NSCLC were enrolled and treated, including 24 males (60%) and 16 females (40%), between January 17, 2023, and June 14, 2024. Pts were aged 43-86 years, with 35 Asians and 5 Caucasians. Twenty-one pts were treatment-naive, while 19 had received prior treatment. As of December 24, 2024, the objective response rate (ORR) in the evaluable population (n=37) was 43.2% (95% CI: 27.10–60.51), with 16 out of 37 patients achieving a response. The median PFS was 15.9 months (95% CI:10.9, NA) for treatment-naive pts and 6.2 months (95% CI:5.9, NA) for previously treated pts. The median follow-up for the efficacy population was 7.7 months. Vabametkib’s safety was assessed in all 40 treated pts, the most common treatment-related adverse events were nausea (n=28; 70%), diarrhea (n=14; 35%), and vomiting (n=8; 20%) and peripheral oedema (n=5; 12.5%). Grade 3 or higher adverse events occurred in 5 (12.5%) pts, no grade 3 edema were reported in the study population (0%). No grade 5 events in this cohort. Conclusions: Vabametkib demonstrates good antitumor activity in pts with METex14 NSCLC, and better toxicity profile with excellent tolerability, compared to FDA-approved MET inhibitors, supporting vabametkib continued clinical development for METex14 NSCLC pts. Clinical trial information: NCT05541822.