1379P - Preliminary results of phase II KUNPENG study of vebreltinib in patients (Pts) with advanced NSCLC harboring c-MET alterations

Background

C-MET alterations implicated as a negative prognostic factor. It can occur as exon 14 (METex14) skipping mutations, gene amplification, and protein overexpression. Vebreltinib (PLB-1001) is a potent highly selective c-MET inhibitor, which has shown promising results in pts with NGS-identified advanced METex14 skipping NSCLC in our previous phase I study. Here we present data from pts with METex14 mutation (Cohort 1) from a phase II, open-label, multicenter and multi-cohort KUNPENG study of PLB1001 conducted in locally advanced or metastatic NSCLC pts with c-MET alterations.

Methods

Eligible pts were ≥18 years of age, ECOG PS 0∼1 with stage IIIB/IV NSCLC. Pts in Cohort 1 received 200 mg of Vebreltinib twice daily (28 days as a cycle) until disease progression, death, AE leading to discontinuation or withdrawal of consent. The primary endpoint was objective response rate (ORR) assessed by blinded independent review committee (BIRC) per RECIST v1.1. Secondary endpoints included investigator-assessed (INV) ORR, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS) and overall survival (OS).

Results

As of 09-Aug-2022, 113 pts were enrolled, among whom 52 pts were in Cohort 1. 32.7% (17/52) pts previously received systematic therapy for advanced or metastatic NSCLC. The primary endpoint ORR was 75% (95% CI: 61.1%∼86.0%) per BIRC, while the ORR was 77.1% (95% CI: 59.9%∼89.6%) in treatment-naïve pts and 70.6% (95% CI: 44.0%∼89.7%) in previously-treated pts. ORR per INV was 69.2% (95% CI: 54.9%∼81.3%), while the ORR was 74.3% (95% CI: 56.7%∼87.5%) in treatment-naïve pts and 58.8% (95% CI: 32.9%∼81.6%) in previously-treated pts. Per BIRC, DCR was 96.2%, median DoR was 15.9 months, median TTR was 1.0 month, median PFS was 14.1 months and median OS was 20.7 months. Among pts with baseline brain metastases (N=5), ORR was 100.0%. The most common (≥20%) TRAEs in all the 113 pts were peripheral edema (56.6%), hypoalbuminemia (22.1%) and hypoproteinemia (19.5%). Most of the TRAEs were grade 1/2.

Conclusions

Vebreltinib showed promising efficacy and favorable safety in patients with METex14 mutant NSCLC.

Clinical trial identification

NCT04258033.

Editorial acknowledgement

Legal entity responsible for the study

Beijing Pearl Biotechnology Co., Ltd. Avistone Biotechnology Limited.

Funding

Beijing Pearl Biotechnology Co., Ltd. Avistone Biotechnology Limited.

Disclosure

All authors have declared no conflicts of interest.