Phase (Ph) I study of the safety and efficacy of the cMET inhibitor capmatinib (INC280) in patients (pts) with advanced cMET+ non-small cell lung cancer (NSCLC).

Schüler, Martin; Berardi, Rossana; Lim, Wan-Teck; Geel, Robin M.J.M. van; Jonge, Maja J. De; Bauer, Todd M.; Azaro, Analía; Gottfried, Maya; Han, Ji‐Youn; Lee, Dong Hoon; Wollner, Mira; Hong, David S.; Vogel, Arndt; Delmonte, Angelo; Krause, Alexander; Zhang, Yong; Squires, Matthew; Giovannini, Monica; Akimov, Mikhail; Bang, Yung‐Jue

doi:10.1200/jco.2016.34.15_suppl.9067

Cited by 48 publications

(49 citation statements)

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“…This phase I, dose‐escalation study was conducted in Japanese patients with advanced solid tumors who had progressed despite standard therapy or for whom no effective therapy exists. The expansion was not initiated because sufficient data for further development were already available from other clinical studies of capmatinib …”

Section: Discussionmentioning

confidence: 99%

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Phase I dose‐escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors

et al. 2019

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Capmatinib is a highly specific, potent and selective MET inhibitor. This was an open‐label, multicenter, dose‐escalation, phase I study conducted in Japanese patients with advanced solid tumors (not selected based on their MET status). The primary objective was to determine the maximum tolerated dose ( MTD ) and/or highest studied dose being safe. Secondary objectives included safety, pharmacokinetics and preliminary antitumor activity. Dose escalation was guided by a Bayesian Logistic Regression Model dependent on dose‐limiting toxicities ( DLT ) in cycle 1. Of 44 adult Japanese patients with confirmed advanced solid tumors enrolled, 29 received capmatinib capsules (doses ranging from 100 mg once daily [q.d.] to 600 mg twice daily [b.i.d.]) and 15 received tablets (200 mg b.i.d. and 400 mg b.i.d.). DLT occurred in two patients: grade 2 suicidal ideation (600 mg b.i.d. capsule) and grade 3 depression (400 mg b.i.d. tablet). MTD was not reached. The highest studied dose determined to be safe as tablet was 400 mg b.i.d., whereas it is not yet determined for capsules. Most common adverse events suspected to be drug‐related were increased blood creatinine, nausea, decreased appetite, vomiting and diarrhea. Following repeated daily dosing up to day 15 by q.d. or b.i.d. regimen using capsules, median time to reach maximum plasma drug concentration ( T max ) was 1.0‐4.0 hours; absorption was more rapid after dosing using tablets, with median T max of 1.0 hour on both days 1 and 15. Eight patients had a best overall response of stable disease. These data support further clinical development of capmatinib.

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Section: Discussionmentioning

confidence: 99%

“…Thus, the RP2D of capmatinib in tablet formulation was stated as 400 mg tablet b.i.d. in the global study …”

Section: Introductionmentioning

confidence: 99%

Phase I dose‐escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors

et al. 2019

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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%

“…In a phase I study of capmatinib, preliminary antitumor activity was seen in patients with EGFR-wild-type NSCLC and a high level of MET amplification (MET GCN !6; ref. 63), while a study of capmatinib plus gefitinib in patients with EGFR-mutant, METpositive NSCLC reported an overall response rate of 50% in patients with MET GCN !6 (64). Although, based on preliminary data, MET GCN appears to be a good predictive biomarker, the FISH MET/chromosome enumeration probe 7 (CEP7) ratio is also a relatively simple primary measure of amplification.…”

Section: Met Amplificationmentioning

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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“…In a phase I study (NCT01324479), relapsed NSCLC patients with high cMET expression were given capmatinib. In subgroup of patients with MET -amplified disease, the ORR was 63%, and the median PFS was 7.4 months [41]. Glesatinib (MGCD265) is another MET blocker currently being studied in NSCLC (NCT00697632).…”

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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Phase (Ph) I study of the safety and efficacy of the cMET inhibitor capmatinib (INC280) in patients (pts) with advanced cMET+ non-small cell lung cancer (NSCLC).

Cited by 48 publications

References 0 publications

Phase I dose‐escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors

Phase I dose‐escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors

MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale

Emerging therapeutic agents for lung cancer

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