A phase I dose-escalation study of INCB028060, an inhibitor of c-MET receptor tyrosine kinase, in patients with advanced solid tumors.

Donehower, Ross C.; Scardina, Angela; Hill, Margaret; Bowman, Jessica; Newton, R. C.; Liu, X.; Scherle, Peggy; Wang, Q.; Diamond, S B; Boer, Jennifer C.; Lee, F.; Gau, Timothy C.; Burris, H. A.; Bendell, J. C.; Jones, Suzanne F.; Infante, J. R.

doi:10.1200/jco.2011.29.15_suppl.3091

Cited by 6 publications

(4 citation statements)

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“…Dose-dependent decreases in Met phosphorylation, monitored by ELISA, are also promising. AEs included mild tremor, fatigue, nausea, diarrhea, indigestion, headache, and agitation 96 .…”

Section: Pharmacological Inhibitors Of the Hgf/met Pathwaymentioning

confidence: 99%

Targeting the HGF/Met signaling pathway in cancer therapy

Cecchi¹,

Rabe²,

Bottaro³

2012

Expert Opinion on Therapeutic Targets

199

177

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Introduction Under normal conditions, hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase (TK), is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis and tumor progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. Area covered The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programs. The authors review Met structure and function, the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development, as well as the latest clinical trial results. Expert opinion Clinical trials with HGF/Met pathway antagonists show that as a class these agents are well tolerated. Although widespread efficacy was not seen in several completed phase 2 studies, promising results have been reported in lung, gastric, prostate and papillary renal cancer patients treated with these agents. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment are optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signaling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control.

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“…Dose-dependent decreases in Met phosphorylation, monitored by ELISA, are also promising. AEs included mild tremor, fatigue, nausea, diarrhea, indigestion, headache, and agitation 96 .…”

Section: Pharmacological Inhibitors Of the Hgf/met Pathwaymentioning

confidence: 99%

Targeting the HGF/Met signaling pathway in cancer therapy

Cecchi¹,

Rabe²,

Bottaro³

2012

Expert Opinion on Therapeutic Targets

199

177

View full text Add to dashboard Cite

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“…Preliminary results of Phase I trial have been published as meeting abstract: the maximum tolerated dose (MTD) has not been reached and no other grade 3/4 AEs were noted. Grade 1 --2 AEs considered possibly as treatment-related include mild tremor, fatigue, nausea, diarrhea, indigestion, headache and agitation [80]. A Phase II study is currently ongoing in patients with pRCC (NCT02019693) who received previous targeted agents including MET inhibitors; the primary end point is the ORR and results are expected in December 2016.…”

Section: Met ± Vegfr Inhibitorsmentioning

confidence: 98%

Emerging tyrosine kinase inhibitors for the treatment of renal cancer

Iacovelli¹,

Albigès²,

Escudier³

2015

Expert Opinion on Emerging Drugs

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Despite the development of more potent and more specific VEGFR TKIs, all tumors ultimately develop resistance to therapy and a plateau has been reached in terms of overall survival. Current research effort to develop new agents aims at overcoming both the primary and the acquired resistance to anti-VEGFR TKIs focusing on new molecular pathways. The ultimate goal is not only to improve patient outcome but to achieve durable complete remission. Several pitfalls that have been responsible for failure of other compounds remain, especially the lack of strong predictive biomarkers and the use of inappropriate tumor assessment criteria that may not accurately capture response to these new therapies.

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“…Oral small-molecule inhibitors of c-Met are currently in phase I trials both as monotherapy and in combination with gemcitabine and sorafenib [74-76]. …”

Section: Introductionmentioning

confidence: 99%

“… Preclinical work examining the role of proto-oncogene c-Met, also known as hepatocyte growth factor receptor, in the pathogenesis of basaloid tumors and trastuzumab-resistant, Her2-positive tumors points to another potential opportunity for targeted therapy [ 9 , 19 , 73 ]. Oral small-molecule inhibitors of c-Met are currently in phase I trials both as monotherapy and in combination with gemcitabine and sorafenib [ 74 - 76 ]. …”

Section: Introductionmentioning

confidence: 99%

Current approaches to the management of Her2-negative metastatic breast cancer

Gogineni

DeMichele

2012

Breast Cancer Res

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While metastatic breast cancer (MBC) remains incurable, a vast array of active therapeutic agents has provided the opportunity for long-term disease control while maintaining quality of life and physical function. Optimal management of MBC balances a multitude of factors, including a woman's performance status, social support, symptoms, disease burden, prior therapies, and surrogates for tumor biology. Choosing the most appropriate initial therapy and subsequent sequence of treatments demands flexibility as goals and patient preferences may change. Knowledge of the estrogen receptor (ER), progesterone receptor (PR), and Her2 receptor status of the metastatic tumor has become critical to determining the optimal treatment strategy in the metastatic setting as targeted therapeutic approaches are developed. Patients with ER+ or PR+ breast cancer or both have a wide array of hormonal therapy options that can forestall the use of cytotoxic therapies, although rapidly progressive phenotypes and the emergence of resistance may ultimately lead to the need for chemotherapy in this setting. So-called 'triple-negative' breast cancer - lacking ER, PR, and Her2 overexpression - remains a major challenge. These tumors have an aggressive phenotype, and clear targets for therapy have not yet been established. Chemotherapy remains the mainstay of treatment in this group, but biologically based clinical trials of new agents are critical to developing a more effective set of therapies for this patient population.

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A phase I dose-escalation study of INCB028060, an inhibitor of c-MET receptor tyrosine kinase, in patients with advanced solid tumors.

Cited by 6 publications

References 0 publications

Targeting the HGF/Met signaling pathway in cancer therapy

Targeting the HGF/Met signaling pathway in cancer therapy

Emerging tyrosine kinase inhibitors for the treatment of renal cancer

Current approaches to the management of Her2-negative metastatic breast cancer

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