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Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter,
Jin-Ji Yang1, Yan Zhang2,3, Lin Wu4
1Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Purpose:
The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations.
Methods:
This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1.
Results:
As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and 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 were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%).
Conclusion:
Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.
Insights
Vebreltinib demonstrated significant efficacy in treating non-small cell lung cancer (NSCLC) with MET alterations. This MET inhibitor showed a high objective response rate and favorable safety in the KUNPENG trial.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- Alterations in the MET signaling pathway, particularly MET exon 14 skipping (METex14), are key oncogenic drivers in a subset of NSCLC patients.
- Targeted therapies inhibiting MET are crucial for improving outcomes in these patients.
Purpose of the Study:
- To evaluate the efficacy and safety of vebreltinib, a selective MET inhibitor, in patients with locally advanced or metastatic NSCLC harboring MET alterations.
- To assess the objective response rate (ORR) and duration of response (DoR) as primary and key secondary endpoints, respectively.
Main Methods:
- A multicenter, single-arm, phase II trial (KUNPENG study) enrolled patients with c-Met dysregulated NSCLC.
- Cohort 1 focused on patients with METex14-mutant NSCLC who were treatment-naïve to MET inhibitors.
- Patients received vebreltinib 200 mg twice daily; outcomes were assessed by an independent review committee per RECIST v1.1.
Main Results:
- The study enrolled 52 patients, with 35 (67.3%) being treatment-naïve.
- An overall objective response rate (ORR) of 75% was observed (77.1% in treatment-naïve, 70.6% in previously treated).
- Median DoR was 15.9 months, median progression-free survival was 14.1 months, and median overall survival was 20.7 months. Common adverse events included peripheral edema and QT prolongation.
Conclusions:
- Vebreltinib exhibits promising efficacy in patients with METex14-mutant NSCLC.
- The drug demonstrates a favorable safety profile, supporting its potential as a treatment option.
- These findings highlight the therapeutic potential of targeting MET alterations in NSCLC.
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