Phase (Ph) II safety and efficacy results of a single-arm ph ib/II study of capmatinib (INC280) + gefitinib in patients (pts) with EGFR-mutated (mut), cMET-positive (cMET+) non-small cell lung cancer (NSCLC).

Wu, Yi‐Long; Kim, Dong-Wan; Felip, Enriqueta; Zhang, Li; Liu, Xiaoqing; Zhou, C.; Lee, Dong Hoon; Han, Ji‐Youn; Krause, Alexander; Lebouteiller, Rachel; Xu, Cindy; Squires, Matthew; Akimov, Mikhail; Tan, Daniel Shao-Weng

doi:10.1200/jco.2016.34.15_suppl.9020

Cited by 44 publications

(34 citation statements)

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“…Although IHC data have been shown to correlate with MET amplification (66), clinical study biomarker data (summarized in Table 4) have not confirmed any clear-cut relationships between MET mutation, amplification, and overexpression, when collectively applied as predictive biomarkers for MET-targeted therapy. IHC-based MET expression has not been a successful biomarker approach in clinical studies of monoclonal antibodies, and current clinical and biomarker data suggest that genetic changes in MET, in particular gene amplification, may be the preferred biomarkers for MET TKI therapy (21,(63)(64)(65). The data summarized in Table 4 also indicate that biomarkers for MET TKI therapy need to be optimized based on not only MET amplification but also MET mutation or translocation status, which constitutes an additional and numerically significant (>4%) molecular subgroup of NSCLC (46).…”

Section: Discussion: Potential Of Met As a Biomarker In Lung Cancermentioning

confidence: 99%

MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

Salgia

2017

Molecular Cancer Therapeutics

130

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MET or hepatocyte growth factor (HGF) receptor pathway signaling mediates wound healing and hepatic regeneration, with pivotal roles in embryonic, neuronal, and muscle development. However, dysregulation of MET signaling mediates proliferation, apoptosis, and migration and is implicated in a number of malignancies. In non-small cell lung cancer (NSCLC), aberrant MET signaling can occur through a number of mechanisms that collectively represent a significant proportion of patients. These include MET or HGF protein overexpression, MET gene amplification, MET gene mutation or fusion/rearrangement, or aberrations in downstream signaling or regulatory components. Responses to MET tyrosine kinase inhibitors have been documented in clinical trials in patients with MET-amplified or METoverexpressing NSCLC, and case studies or case series have shown that MET mutation/deletion is a biomarker that is also predictive of response to these agents. However, other recent clinical data have highlighted an urgent need to elucidate optimal biomarkers based on genetic and/or protein diagnostics to correctly identify patients most likely to benefit in ongoing clinical trials of an array of MET-targeted therapies of differing class. The latest advances in the development of MET biomarkers in NSCLC have been reviewed, toward establishing appropriate MET biomarker selection based on a scientific rationale. Mol Cancer Ther; 16(4); 555-65.Ó2017 AACR.

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Section: Discussion: Potential Of Met As a Biomarker In Lung Cancermentioning

confidence: 99%

MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

Salgia

2017

Molecular Cancer Therapeutics

130

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“…An ORR of 18%, an SD of 62%, and a DCR of 80% were observed in 65 evaluable patients. More responses were seen in tumors with MET amplifications [42]. Tepotinib (MSC2156119J) with gefitinib was well tolerated in a phase 1 study (NCT01982955).…”

Section: Targeted Agentsmentioning

confidence: 99%

Emerging therapeutic agents for lung cancer

et al. 2016

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Lung cancer continues to be the most common cause of cancer-related mortality worldwide. Recent advances in molecular diagnostics and immunotherapeutics have propelled the rapid development of novel treatment agents across all cancer subtypes, including lung cancer. Additionally, more pharmaceutical therapies for lung cancer have been approved by the US Food and Drug Administration in the last 5 years than in previous two decades. These drugs have ushered in a new era of lung cancer managements that have promising efficacy and safety and also provide treatment opportunities to patients who otherwise would have no conventional chemotherapy available. In this review, we summarize recent advances in lung cancer therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to drugs in their class or are a completely new class of drugs with novel mechanisms of action. We have divided our discussion into targeted agents, immunotherapies, and antibody drug conjugates for small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). We briefly review the emerging agents and ongoing clinical studies. We have attempted to provide the most current review on emerging therapeutic agents on horizon for lung cancer.

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“…Initial results of combination therapy with gefitinib and the MET inhibitor campmatinib (INC280) in EGFRmutated NSCLC patients who had progressed on prior TKI therapy demonstrated a disease control rate of 80%. Patients with a MET copy number of at least 6 had a higher response rate of 30% versus 19% in those with a copy number of at least 5 (89). Similarly, the MET inhibitor tepotinib in combination with gefinitib has shown promising results (90).…”

Section: Bypass Pathwaysmentioning

confidence: 99%