Telisotuzumab Vedotin Plus Osimertinib Demonstrates Promise for Patients With Advanced, EGFR-Mutated Non-Small Cell Lung Cancer With C-Met Overexpression

According to results from a phase 1/1b trial, the addition of telisotuzumab vedotin to osimertinib demonstrated promise among patients with advanced, non-squamous epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with c-Met protein overexpression. 

“Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC… however, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance,” stated Hidehito Horinouchi, MD, PhD, National Cancer Center Hospital, Tokyo, Japan, and coauthors. “Telisotuzumab vedotin is an antibody-drug conjugate that targets c-Met protein overexpression.” 

In this multicenter, open-label study, 38 patients with advanced, non-squamous EGFR-mutated NSCLC with c-Met protein overexpression who experienced disease progression after osimertinib were assigned to receive either 1.6 mg/kg (n = 20) or 1.9 mg/kg (n = 18) of telisotuzumab vedotin once every 2 weeks plus 80 mg of daily osimertinib. Primary end points included objective response rate (ORR), duration of response, progression-free survival (PFS), and safety. 

At a median follow-up of 7.4 months, the ORR was 50% and the duration of response was not reached. The median PFS was 7.4 months. The most common treatment-emergent adverse events included peripheral sensory neuropathy (50%), peripheral edema (32%), and nausea (24%). The most common grade 3/4 treatment-emergent adverse events included anemia (11%) and pulmonary embolism (8%). No dose-limiting toxicities were reported. 

“[Telisotuzumab vedotin] plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein–overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib,” concluded Dr Horinouchi et al. “This combination has the potential to address an unmet medical need in this patient population.”

Source: 

Horinouchi H, Cho BC, Camidge DR, et al. Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein–overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib. Ann Oncol. Published online: January 11, 2025. doi: 10.1016/j.annonc.2025.01.001