Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study

Purpose: The KUNPENG study was designed to assess the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with c-Met alterations.

Methods: This multicenter, open-label, single-arm, phase II trial involved patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 consisted of patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously been treated with MET inhibitors. Participants received vebreltinib at 200 mg twice daily in 28-day cycles. The primary endpoint was the objective response rate (ORR), and the key secondary endpoint was the duration of response (DoR), both assessed by a blinded independent review committee according to RECIST version 1.1.

Results: As of August 9, 2022, 52 patients were enrolled in cohort 1, with 35 (67.3%) being treatment-naïve. The ORR was 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), while in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events included peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%).

Conclusion: Vebreltinib demonstrates significant efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.