Safety and efficacy of INC280 in combination with gefitinib (gef) in patients with <i>EGFR</i>-mutated (mut), MET-positive NSCLC: A single-arm phase lb/ll study.

Wu, Yi‐Long; Yang, James Chih‐Hsin; Kim, Dong-Wan; Su, Wu‐Chou; Ahn, Myung‐Ju; Lee, Dong Hoon; Vansteenkiste, Johan; Zhang, Li; Felip, Enriqueta; Peng, Bin; Gong, Ying; Zhao, Sylvia; Amagasaki, Taro; Akimov, Mikhail; Tan, Daniel Shao-Weng

doi:10.1200/jco.2014.32.15_suppl.8017

Cited by 44 publications

(43 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Partial responses were observed in 15% patients (6/41), all with high MET status (NCT01610336) [165]. Another phase I study is currently testing capmatinib in combination with erlotinib in NSCLC patients (NCT01911507).…”

Section: Selective Met Inhibitorsmentioning

confidence: 99%

MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung cancer

Pérez-Ramírez

Cañadas-Garre

Molina

et al. 2015

Pharmacological Research

View full text Add to dashboard Cite

Section: Selective Met Inhibitorsmentioning

confidence: 99%

MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung cancer

Pérez-Ramírez

Cañadas-Garre

Molina

et al. 2015

Pharmacological Research

View full text Add to dashboard Cite

“…There are several ongoing clinical trials of MET TKIs or MET MAbs in combination with EGFR TKIs with the majority of studies selecting for patients that are MET positive by various assays (Table 3). An ongoing phase 1 study of INC280 and gefitinib in EGFR mutant patients with AR who have either MET amplification or MET overexpressionhas modest activity, with a 15% unconfirmed RR (6/41 patients)(47). In addition to MET amplification, MET activation through increased production of HGF is a potential mechanism of resistance to EGFR TKIs (48).…”

Section: Therapeutic Strategies Targeting Alternate Pathwaysmentioning

confidence: 99%

Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

Riely

Lovly

2014

Clinical Cancer Research

View full text Add to dashboard Cite

Patients with EGFR mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways, such as MET and HER2. Several therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including ‘next-generation’ EGFR TKIs and rational combinations of targeted agents. However, to date, there are no FDA approved therapies for patients with acquired resistance to first-line EGFR TKI therapy. There remains a critical need for more effective and better tailored treatments in this setting in order to match treatments to the individual patient and specific resistance mechanism at hand. In this review, we will discuss known mechanisms of resistance to first-line EGFR TKI therapy and describe previous and ongoing strategies to overcome resistance.

show abstract

“…Overall response rates were 40% in patients with MET CN ≥5 and 38% in patients with MET IHC staining intensity of 3+ [76]. Unexpectedly, some NSCLCs with high MET expression (IHC 3+) and amplification exhibited tumor progression following treatment.…”

Section: Biomarker Validation In Met Inhibitor Clinical Trialsmentioning

confidence: 99%

Biomarker development in MET-targeted therapy

Zhang¹,

Du²,

Zhang³

2016

Oncotarget

View full text Add to dashboard Cite

Activation of the MET receptor tyrosine kinase by its ligand, hepatocyte growth factor (HGF), has been implicated in a variety of cellular processes, including cell proliferation, survival, migration, motility and invasion, all of which may be enhanced in human cancers. Aberrantly activated MET/HGF signaling correlates with tumorigenesis and metastasis, and is regarded as a robust target for the development of novel anti-cancer treatments. Various clinical trials were conducted to evaluate the safety and efficacy of selective HGF/MET inhibitors in cancer patients. There is currently no optimal or standardized method for accurate and reliable assessment of MET levels, or other biomarkers that are predictive of the patient response to MET-targeted therapeutics. In this review, we discuss the importance of accurate HGF/MET signal detection as a predictive biomarker to guide patient selection for clinical trials of MET-targeted therapies in human cancers.

show abstract

Safety and efficacy of INC280 in combination with gefitinib (gef) in patients with EGFR-mutated (mut), MET-positive NSCLC: A single-arm phase lb/ll study.

Cited by 44 publications

References 0 publications

MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung cancer

MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung cancer

Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

Biomarker development in MET-targeted therapy

Contact Info

Product

Resources

About