New Progress of the KUNPENG Study: Research Findings on Vebreltinib for Advanced NSCLC with MET Amplification Presented at the 2025 ESMO Asia Congress

The ESMO Asia Congress 2025 is ongoing in Singapore from December 5 to 7, 2025. At this annual meeting, Avistone announced the results of the Phase II clinical trial "Vebreltinib for the Treatment of Advanced NSCLC with MET Amplification (the KUNPENG Study)", which was led by Professor Wu Yilong from the Guangdong Lung Cancer Institute.

 01  976 MO

Presentation Type: Mini Oral Session
Presentation Title: Vebreltinib in MET amplification-driven advanced non-small-cell lung cancer (NSCLC): Results from phase 2 KUNPENG study

Presentation Time: December 6, 2025, 16:15 – 16:20 (Local Time)

Venue: HALL 406

Speaker: Wu Yilong (Guangdong Lung Cancer Institute)

 02    Core Information Flash

Background
      

Targeted therapy has achieved breakthrough progress in the treatment of non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (AGA). However, MET amplification-driven NSCLC still poses formidable challenges. This subset accounts for 1%–5% of all NSCLC cases and is associated with a poor prognosis [1]. Previous studies have shown that the objective response rate (ORR) of small-molecule MET inhibitors in chemotherapy-pretreated MET-amplified NSCLC patients ranges only from 7% to 32%, indicating suboptimal efficacy [1, 2]. Therefore, large-sample, prospective clinical studies are urgently needed to validate the clinical value of MET amplification as a therapeutic target and further explore more effective treatment agents. As a highly selective MET inhibitor, Vebreltinib has demonstrated promising antitumor activity against advanced NSCLC with MET alterations in a Phase I trial and the preliminary analysis of the Phase II KUNPENG study [1, 3]. The full Phase II study data presented at the ESMO ASIA 2025 Annual Congress further confirmed the significant clinical potential of this agent.

Study Design
       

         The KUNPENG study is a multicenter, multi-cohort, open-label, single-arm Phase II clinical trial with the following design [1]:

Eligible Population: Patients aged ≥18 years with histologically or cytologically confirmed Stage ⅢB–Ⅳ NSCLC, positive for MET amplification (FISH assay, GCN ≥ 6), and negative for EGFR mutation, ALK/ROS1 rearrangement, and KRAS mutation. A total of 86 patients were enrolled, including 30 in the pretreated cohort and 56 in the treatment-naive cohort.

Treatment Regimen: Vebreltinib 200 mg, orally administered twice daily, until disease progression or intolerable toxicity.

Primary Endpoint: Objective response rate (ORR) assessed by the Blinded Independent Review Committee (BIRC).
 

Key Data (Data Cut-off: November 14, 2024)

Efficacy Data (See Table 1 for Details)

Objective Response Rate (ORR): The ORR in the overall population reached 48.8% (95% CI: 38.3–59.4, n=86). Specifically, the ORR was 43.3% in the pretreated cohort (95% CI: 25.6–61.1, n=30) and as high as 51.8% in the treatment-naive cohort (95% CI: 38.7–64.9, n=56).

Disease Control Rate (DCR): The DCR in the overall population was 77.9% (95% CI: 69.1–86.7, n=86). The pretreated cohort had a DCR of 73.3% (95% CI: 57.5–89.2, n=30), while the treatment-naive cohort achieved a DCR of 80.4% (95% CI: 70.0–90.8, n=56).

Duration of Response (DoR): The median DoR in the overall population was 12.1 months (95% CI: 6.5–16.8, n=86). The pretreated cohort had a median DoR of 11.0 months (95% CI: 3.7–NE, n=30), and the treatment-naive cohort showed a median DoR consistent with the overall population (12.1 months, 95% CI: 5.4–16.8, n=56).

Table 1  Efficacy Analysis Results

Safety Data (See Figure 1 for Details)

•  The incidence of treatment-related adverse events (TRAEs) of Grade 3 or higher was only 31.4% (n=86).
•  The most common TRAEs were peripheral edema (44.2%) and hypoalbuminemia (33.7%), with most being Grade 1 or 2.

Figure 1 Safety Analysis Results

Study Conclusions

        Results from the Phase II KUNPENG study demonstrated that Vebreltinib exhibited significant antitumor activity with a manageable safety profile in patients with MET-amplified advanced NSCLC who were naive to MET inhibitors, regardless of whether they were treatment-naive or pretreated [1].

References

1. Wu Y-L, et al. Vebreltinib in MET amplification-driven advanced NSCLC (KUNPENG). Presented at ESMO Asia Congress 2025, Singapore, Dec 6, 2025.

2. Wolf J, et al. Capmatinib in MET Exon 14-Mutated or MET-Amplified NSCLC. N Engl J Med 2020; 383(10): 944-957.

3.Yang J-J, et al. Vebreltinib for NSCLC with c-Met Exon 14 Skipping Mutation. J Clin Oncol 2024; 42(31): 3680-3691.

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