Avistone Biotechnology has announced promising results from a clinical research program evaluating the combination of vebreltinib, a c-MET inhibitor, and PLB1004, an EGFR inhibitor, in patients with non-small cell lung cancer (NSCLC). The data, presented at the 2024 World Conference on Lung Cancer (WCLC) in San Diego, CA, suggest a potential benefit for patients with EGFR-mutated NSCLC who have MET amplification or overexpression.
Study Design and Patient Population
The study, identified by Clinical Trial Identifier NCT06343064, involved 44 patients who received varying doses of vebreltinib (100mg, 150mg, or 200mg) in combination with PLB1004 (80mg or 160mg). A significant portion of the patients had challenging disease characteristics: 36.4% had brain metastases, and 86.4% had previously been treated with a third-generation EGFR-TKI.
Efficacy Outcomes
The combination therapy demonstrated encouraging efficacy. Among the 32 response-evaluable patients, the objective response rate (ORR) was 59.4%, with partial responses (PRs) observed. Notably, the ORR was particularly high (75.0%) in the subgroup of patients with brain metastases (9 out of 12 patients). Furthermore, in patients who had previously received a third-generation EGFR-TKI, the ORR was 58.6% (17 out of 29 patients).
Safety Profile
The safety profile of the combination was manageable. The most common treatment-related adverse events (TRAEs) were rash and paronychia. Importantly, no patients discontinued treatment due to TRAEs.
Implications and Future Directions
"The development of drugs for indications related to both c-MET and EGFR targets has always been a difficult one. We are now entering an era where the clinical combination of these targets has shown meaningful potential benefit to patients with NSCLC," said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone. These preliminary results suggest that the combination of vebreltinib and PLB1004 could offer a new treatment option for NSCLC patients with EGFR mutations and MET alterations, particularly those with brain metastases or those who have progressed on prior EGFR-TKI therapy. Further studies are warranted to confirm these findings and to optimize the dosing regimen.
