2026 WCLC | Poster: Exploratory Analysis of the KUNPENG Study of Vebreltinib in MET-Amplified NSCLC: c-MET Overexpression as a Potential Biomarker

At the 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea, the KUNPENG study of Vebreltinib (万比锐®), led by Professor Yi-Long Wu's team at Guangdong Provincial People's Hospital, presented an exploratory analysis during the poster session. Biomarker analysis of the Phase II study showed that c-MET protein overexpression (IHC 3+ or H-score ≥240) may serve as a potential biomarker for predicting the efficacy in MET amplification-driven non-small cell lung cancer (NSCLC) ^[1].

01

PART ONE

Poster

Poster P2.246

Poster title: c-MET Overexpression as an Efficacy Predictive Biomarker in MET Amplification-Driven NSCLC: Explore Analyses of the KUNPENG Study

Principal investigators: Si-Yang Maggie Liu (first author), Yi-Long Wu (corresponding author), et al.

Collaborating centers: Guangdong Provincial People's Hospital, Guangdong Lung Cancer Institute, Southern Medical University, The First Affiliated Hospital of Xi'an Jiaotong University, Hunan Cancer Hospital, Shanghai Chest Hospital, Jilin Cancer Hospital, Fujian Cancer Hospital, etc.

Congress: 2026 World Conference on Lung Cancer (WCLC), Seoul, South Korea

Poster session: 14 September 2026, 10:30–12:00

Location: Exhibits and Posters, Hall C, 3F

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PART TWO

Background

MET amplification is an actionable driver alteration in NSCLC and is closely associated with poor prognosis ^[2-4]. Previous studies showed that MET-Amplified NSCLC patients receiving standard chemotherapy/immunotherapy had a median progression-free survival (PFS) of 2.5–4.9 months ^[5,6]. Vebreltinib is an oral, highly selective MET inhibitor which has been granted conditional approval by the National Medical Products Administration (NMPA) of China for patients with locally advanced or metastatic NSCLC harboring MET exon 14 skipping mutation and MET amplification ^[7,8]. In the Phase II KUNPENG study, Vebreltinib achieved a median PFS of 7.4 months in patients with MET-amplified locally advanced or metastatic NSCLC ^[9], with results published in The Lancet Oncology in December 2025. At this congress, exploratory analyses were presented to investigate whether c-MET immunohistochemistry (IHC) overexpression could further identify patients most likely to benefit.

Treatment benefit among patients with MET-amplified NSCLC is highly heterogeneous, and biomarkers to identify those most likely to benefit from highly selective MET inhibitors remain lacking. Moreover, FISH (fluorescence in situ hybridization), the gold-standard test for MET amplification, is limited by accessibility and cost; more convenient and accessible assays are needed to aid patient selection. This exploratory analysis aimed to evaluate the correlation between c-MET protein expression level (IHC staining intensity and H-score) and Vebreltinib efficacy, providing preliminary evidence for precision stratification in the MET-amplified population. 

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PART THREE

Study Design & Efficacy

This analysis was based on the MET-amplified cohort of the Phase II KUNPENG study. FISH positivity was defined as gene copy number (GCN) ≥6. A total of 136 patients with adequate tissue sections underwent IHC staining for c-MET protein expression; pathologists evaluated the percentage of stained tumor cells, staining intensity (1+, 2+, 3+), and calculated H-score. Eighty-two patients who received Vebreltinib (200 mg orally twice daily) were stratified by c-MET expression level for efficacy analysis. The maximally-selected rank test was used to systematically screen H-score cutoffs from 140 to 250 in increments of 10.

Efficacy Results

• IHC and FISH results showed concordant trends: Among MET amplification-positive patients, 78.3% showed c-MET IHC 3+ or 2+ expression, compared with 36.0% of MET amplification-negative patients (P<0.0001); among 27 patients with IHC 3+ staining, 26 were confirmed  MET amplification-positive by FISH. The same trend was observed in patients with an IHC H-score ≥240.
• Patient benefit increased with rising c-MET protein expression: Twelve patients (14.0%) with c-MET overexpression (IHC 3+) achieved an objective response rate (ORR) of 66.7%, a disease control rate (DCR) of 100%, a median progression-free survival (mPFS) of 13.6 months, and a median overall survival (mOS) of 13.9 months. In patients with MET overexpression defined as an H-score ≥240 (n=15, 18.3%) ,the ORR was 73.3%, the DCR was 100%, mPFS was 12.0 months, and mOS was 17.1 months.
• The correlation between benefit and c-MET protein expression was more pronounced in treatment-naïve patients: In treatment-naïve patients, ORR increased progressively with rising c-MET protein expression: 23.1%, 58.1%, 61.5%, and 75.5% in the IHC ≤1, 2+, 2+/3+, and 3+ subgroups, respectively. However, in previously treated patients, this upward trend was less obvious. H-score-based analyses showed consistent results between treatment-naïve and previously treated patients across different H-score levels.
• Patients with MET polysomy detected by FISH also benefited: Ten patients (11.6%) with chromosome 7 polysomy (GCN ≥6 and MET/CEP7 <2) achieved an ORR of 60.0%, an mPFS of 9.2 months, and an mOS of 18.0 months, suggesting that this subgroup may also benefit from Vebreltinib. Benefit in this subgroup was significantly heterogeneous; possible mechanisms include c-MET protein overexpression or tumor tissue heterogeneity that may obscure focal amplification in polysomy patients.

Table 1 Efficacy analysis of Vebreltinib by c-MET IHC expression level and MET polysomy

Note: NE, not estimable. Two patients in the IHC 3+ subgroup were lost to follow-up at an early time point.

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PART FOUR

Conclusions

Exploratory analyses of the KUNPENG study indicate that c-MET protein overexpression (IHC 3+ or H-score ≥240) may serve as a predictive biomarker for Vebreltinib efficacy in MET-amplified NSCLC, particularly in  treatment-naïve patients. Patients with MET polysomy (GCN ≥6 and MET/CEP7 <2) may also derive benefit from treatment. The investigators recommend that c-MET IHC overexpression (3+ or H-score ≥240) be incorporated as a stratification factor alongside MET amplification in future MET-TKI clinical trials, and that prospective cohort studies be conducted to further validate its predictive value.

References

1. Liu S-YM, Yao Y, Yang J-J, et al. c-MET Overexpression as an efficacy predictive biomarker in MET amplification-driven NSCLC: exploratory analyses of the KUNPENG study. Poster P2.246. Poster session: 10:30 local time, 14 September 2026. 2026 World Conference on Lung Cancer (WCLC), Seoul, South Korea.
2. Mountzios G, et al. MET alterations in NSCLC — Current Perspectives and Future Challenges. J Thorac Oncol. 2023;18(4):419-435.
3. Tong JH, Yeung SF, Chan AW, et al. MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis. Clin Cancer Res. 2016;22(12):3048-3056.
4. Sterlacci W, Fiegl M, Gugger M, et al. MET Overexpression and gene amplification: prevalence, clinico-pathological characteristics and prognostic significance in a large cohort of patients with surgically resected NSCLC. Virchows Arch. 2017;471:49-55.
5. Zhang Y, Yang Q, Zeng X, et al. MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING. Cancer Discov. 2021;11(11):2726-2737.
6. Dudnik E, Bshara E, Grubstein A, et al. Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi). Lung Cancer. 2018;124:117-124.
7. https://www.nmpa.gov.cn/zhuanti/cxylqx/cxypxx/20231116102348157.html
8. https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20250630161536179.html
9. Wu Y, Yao Y, Yang J, et al. Vebreltinib in MET amplification-driven advanced non-small-cell lung cancer (KUNPENG): a single-arm, multi-cohort, multicentre, phase 2 study. The Lancet Oncology. 2026;27(1):36-44.

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