FGFR Inhibitor Dovitinib Shows Modest Efficacy in Squamous NSCLC

Excerpt:

“The FGFR inhibitor dovitinib showed modest efficacy in a phase II trial of patients with pretreated, advanced squamous cell carcinoma (SCC) of the lung with FGFR1 amplification. Further work on the drug, in particular to find biomarkers of efficacy, was deemed warranted.

“ ‘The majority of new cytotoxic chemotherapies for the treatment of non–small-cell lung cancer (NSCLC) such as pemetrexed or targeted agents such as gefitinib or erlotinib are not indicated for the SCC subtype because of a lack of efficacy or because activity is limited to tumors with specific genetic alterations that are rarely found in patients with squamous cell NSCLC,’ wrote study authors led by Myung-Ju Ahn, MD, PhD, of Samsung Medical Center in Seoul, South Korea. SCC accounts for about 30% of all NSCLC cases.”

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Investigational Compound Targets FGFR Pathway

“A novel selective inhibitor of the FGFR pathway yielded a 33% response rate in a small cohort of patients with gastroesophageal cancer, according to findings presented at the ASCO Annual Meeting.

“Elizabeth Catherine Smyth, MD, clinical research fellow in the gastrointestinal and lymphoma department at The Royal Marsdenin London, and colleagues investigated AZD4547 (AstraZeneca) — a selective inhibitor of FGFR 1, 2 and 3 receptor tyrosine kinases — in patients with FGFR1/2-amplified cancers.

“ ‘The FGFR signaling pathway plays a key role in oncogenesis,’ Smyth said during the presentation. ‘The nature and frequency of FGFR pathway abnormalities varies frequently between tumor types. The focus of this study is on FGFR-amplified tumors.’

“Smyth and colleagues screened 285 patients with advanced cancer and identified FGFR1 amplification in 18% (n = 20 of 111) of patients with HER-2–negative breast cancer and 9.5% (n = 4 of 42) of patients with non–small cell lung cancer, as well as FGFR2 amplification in 7.6% (n = 10 of 132) of patients with gastroesophageal cancer.”


Clovis Oncology Announces First Patient Enrolled in Lucitanib Phase 2 Study in FGF-aberrant Advanced Breast Cancer

The gist: The first patient has been enrolled in a new clinical trial—a research study with volunteer patients. The trial is testing whether a drug called lucitanib can be used to treat people with advanced breast cancer. Specifically, the drug will be tested in patients whose tumors have certain mutations in “FGF pathway” genes. By testing different amounts of the drug in different patients, the researchers hope to be able to determine the best dosage of lucitanib for patients.

“Clovis Oncology (CLVS) today announced that its Phase 2 study of lucitanib in patients with FGF-aberrant, advanced breast cancer has commenced and the first patient dosed at a U.S. study site. Lucitanib is the Company’s oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 and 2 (FGFR1-2), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFR α-ß).

“ ‘Early lucitanib data are encouraging, and suggest that determination of genetic alterations in the FGF pathway may be important to identify the patients most likely to benefit from lucitanib treatment,’ said Professor Carlos L. Arteaga, MD, Associate Director for Clinical Research, Director of the Center for Cancer Targeted Therapies, and Director of the Breast Cancer Program at the Vanderbilt-Ingram Cancer Center of Vanderbilt University. ‘This study will further explore two doses of lucitanib in patients with FGF-aberrant breast cancer, a population which possesses these genetic alterations, and for whom new treatment options are needed.’ ”


Squamous Lung Cancer ‘Master Protocol’ Brings Cancer Research into the 21st Century


Clinical trials help determine whether new cancer treatments are safe and effective, and they provide access to cutting-edge drugs that patients wouldn’t otherwise be able to have. But the clinical trial system is notoriously inefficient, slow, expensive, and laborious. Now, a new and ambitious clinical trial design called the Lung Cancer Master Protocol seeks to overhaul the system, promising to benefit patients and drug companies alike. Continue reading…


Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma

In lung squamous cell carcinoma (lung SCC), one of the most frequently altered receptor tyrosine kinase families is the fibroblast growth factor receptor (FGFR) family, with amplification or mutation observed in all four family members. Here, we describe the oncogenic nature of mutations observed in FGFR2 and FGFR3. We show that several of these mutations drive cellular transformation. Transformation can be reversed by small-molecule FGFR inhibitors currently being developed for clinical use.


Molecular Mechanism of SSR128129E, an Extracellularly Acting, Small-Molecule, Allosteric Inhibitor of FGF Receptor Signaling

The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor…”


Molecular Mechanism of SSR128129E, an Extracellularly Acting, Small-Molecule, Allosteric Inhibitor of FGF Receptor Signaling

The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor…”


Molecular Mechanism of SSR128129E, an Extracellularly Acting, Small-Molecule, Allosteric Inhibitor of FGF Receptor Signaling

The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor…”