Vebreltinib Demonstrated Promising Efficacy, Safety Among Patients With Advanced METex14-Mutant Non-Small Cell Lung Cancer

According to results from the multicenter, multi-cohort, phase 2 KUNPENG trial, vebreltinib, a potent and highly selective c-mesenchymal-epithelial transition (MET) inhibitor, showed promising efficacy and safety among patients with locally advanced or metastatic METex14-mutant non-small cell lung cancer (NSCLC).

Jin-Ji Yang, MD, Guangdong Lung Cancer Institute, Guangzhou, China, and coauthors, highlighted the “imperative for treatment options [for patients with NSCLC harboring the METex14 alteration] at balance efficacy with a manageable safety profile.” In previous phase 1 studies with vebreltinib in this patient population, they noted, “outcomes revealed an ORR of 66.7% alongside a tolerable safety profile.”

In cohort 1 of this open-label, single-arm trial, 52 patients with c-MET dysregulated locally advanced or metastatic NSCLC, naïve to c-Met inhibitor therapies, were assigned to receive 200 mg of vebreltinib twice daily in 28-day cycles until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Key secondary end points included disease control rate, duration of response (DOR), time to response, progression-free survival (PFS), and overall survival (OS). 

At the data cutoff point, confirmed ORR was 75% and disease control rate was 96.2%. With a median treatment span of 9.9 months, time to response was 1 month, median DOR was 15.9 months, and median PFS was 14.1 months. After a median follow-up duration of of 19.4 months, median OS was 20.7 months. Grade ≥3 treatment-related adverse events were observed in 48.1% of patients and most frequently included peripheral edema (13.5%), abnormal liver function (9.6%), elevated alanine aminotransferase (7.7%), elevated aspartate aminotransferase (5.8%), anemia (5.8%), and infectious pneumonitis (5.8%). Study authors also noted, due to the limited sample size “vebreltinib's safety profile warrants further validation in larger-scale studies.”

“The KUNPENG study offers evidence of vebreltinib's efficacy and safety for patients with locally advanced or metastatic METex14-positive NSCLC, highlighting its capacity to induce robust and durable responses alongside a favorable safety profile,” concluded Dr Yang et al. 

“These preliminary results justify additional studies,” added Journal of Clinical Oncology Associate Editor Thomas E. Stinchcombe, MD, Duke Cancer Center, Durham, North Carolina.

Source: 

Yang JJ, Zhang Y, Wu L, et al. Vebreltinib for advanced non–small cell lung cancer harboring c-met exon 14 skipping mutation: A multicenter, single-arm, phase II KUNPENG study. J Clin Oncol. Published online: July 26, 2024. doi: 10.1200/JCO.23.02363