Reference Detail

Ref Type

Journal Article

PMID

(31622732)

Authors

Scagliotti G, Moro-Sibilot D, Kollmeier J, Favaretto A, Cho EK, Grosch H, Kimmich M, Girard N, Tsai CM, Hsia TC, Brighenti M, Schumann C, Wang XA, Wijayawardana SR, Gruver AM, Wallin J, Mansouri K, Wacheck V, Chang GC

Title

A Randomized-Controlled Phase 2 Study of the MET Antibody Emibetuzumab in Combination with Erlotinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer	15	1	2020 Jan	80-90	J Thorac Oncol

URL

Abstract Text

The hepatocyte growth factor receptor mesenchymal-epithelial transition (MET) is reported to be a negative prognostic marker in EGFR-mutant NSCLC and involved in resistance to EGFR inhibitors. Emibetuzumab, a humanized immunoglobulin G4 monoclonal bivalent MET antibody, blocks ligand-dependent and ligand-independent hepatocyte growth factor/MET signaling. This phase 2 study compared erlotinib with and without emibetuzumab in first-line treatment of EGFR-mutant metastatic NSCLC.Patients with stage IV EGFR-mutant NSCLC and disease control after an 8-week lead-in with erlotinib (150 mg daily) were randomized to continue taking erlotinib with or without emibetuzumab (750 mg every 2 weeks). The primary end point was progression-free survival (PFS). Additional end points included overall survival, overall response rate, safety, pharmacokinetics, and exploratory analysis of MET expression.No significant difference in median PFS was observed in the intent-to-treat population (9.3 months with emibetuzumab + erlotinib versus 9.5 months with erlotinib monotherapy [hazard ratio (HR) = 0.89, 90% confidence interval (CI): 0.64-1.23]). The median overall survival was 34.3 months with emibetuzumab plus erlotinib versus 25.4 months with erlotinib (HR = 0.74, 90% CI: 0.49-1.11). Emibetuzumab plus erlotinib was well tolerated, with peripheral edema and mucositis as the only adverse events occurring 10% or more frequently relative to erlotinib. Exploratory post hoc analysis showed an improvement of 15.3 months in median PFS for the 24 patients with the highest MET expression (MET expression level of 3+ in ≥90% of tumor cells) (20.7 with emibetuzumab + erlotinib versus 5.4 months with erlotinib [HR = 0.39, 90% CI: 0.17-0.91]).No statistically significant difference in PFS was noted in the intent-to-treat population. Exploratory analysis confirmed that high MET expression is a negative prognostic marker for patients treated with erlotinib, indicating that emibetuzumab plus erlotinib may provide clinically meaningful benefit.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Emibetuzumab	Emibetuzumab	0	2

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Emibetuzumab		LY2875358	MET Antibody 28 MET Inhibitor 59	Emibetuzumab (LY2875358) is MET-targeted antibody, which inhibits binding of the MET ligand HGF and promotes internalization and downregulation of MET, resulting in decreased HGF-dependent and HGF-independent signaling and potentially leading to decreased growth of MET-expressing tumors (PMID: 27803065, PMID: 25231402, PMID: 31622732).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References