“Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) presented data from the ongoing Phase Ib/II clinical trial of sulfatinib in patients with advanced neuroendocrine tumors (“NET”) at the 14th Annual Conference of European Neuroendocrine Tumor Society (“ENETS”), held in Barcelona, Spain from March 8 to 10, 2017. Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively targets vascular endothelial growth factor receptor (“VEGFR”), fibroblast growth factor receptor (“FGFR”) and colony-stimulating factor-1 receptor (“CSF-1R”), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Five other sulfatinib clinical trials are underway in China and the US, including two Phase III studies in NET patients (SANET-p and SANET-ep), one Phase II study in thyroid cancer patients and one Phase II study in biliary tract cancer patients.”
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.’ ”
Editor’s note: This article covers the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test the effectiveness of adding a drug called ramucirumab (aka Cyramza) to treatment with the chemotherapy drug docetaxel. The patients who participated all had non-small cell lung cancer (NSCLC) that had worsened during platinum-based chemotherapy. The researchers found that ramucirumab provided patients with a small but significant improvement in survival time.
“In the phase III REVEL trial reported in The Lancet, Garon et al found that the addition of the antiangiogenic VEGFR-2 inhibitor ramucirumab (Cyramza) to docetaxel produced a statistically significant improvement in overall survival as second-line treatment in patients with stage IV non–small cell lung cancer (NSCLC) after progression on platinum-based therapy…
“In this double-blind trial, 1,253 patients with squamous or nonsquamous stage IV NSCLC from academic medical centers and community clinics in 26 countries on six continents were randomly assigned between December 2010 and January 2013 to receive docetaxel at 75 mg/m² and either ramucirumab at 10 mg/kg (n = 628) or placebo (n = 625) on day 1 of 21-day cycles until disease progression, unacceptable toxicity, withdrawal, or death. Patients had to have progressed during or after a single platinum-based chemotherapy regimen, with or without bevacizumab (Avastin) or maintenance therapy.
“Randomization was stratified by sex, region, performance status, and previous maintenance therapy. The primary endpoint was overall survival in the intent-to-treat population.”
Dai J, Zhang H, Karatsinides A, Keller JM, et al. Clinical Cancer Research. Oct 4, 2013.
“Purpose: Cabozantinib, an orally available multi-tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2 (VEGFR2), induces resolution of bone scan lesions in men with castration-resistant prostate cancer bone metastases. The purpose of this study was to determine whether cabozantinib elicited a direct anti-tumor effect, an indirect effect through modulating bone, or both. Experimental Design: Using human prostate cancer xenograft studies in mice we determined cabozantinib’s impact on tumor growth in soft tissue and bone. In vitro studies with cabozantinib were performed using (1) prostate cancer cell lines to evaluate its impact on cell growth, invasive ability and MET and (2) osteoblast cell lines to evaluate its impact on viability and differentiation and VEGFR2. Results: Cabozantinib inhibited progression of multiple prostate cancer cell lines (Ace-1,C4-2B, and LuCaP 35) in bone metastatic and soft tissue murine models of prostate cancer, except for PC-3 prostate cancer cells in which it inhibited only subcutaneous growth. Cabozantinib directly inhibited prostate cancer cell viability and induced apoptosis in vitro and in vivo and inhibited cell invasion in vitro. Cabozantinib had a dose-dependent biphasic effect on osteoblast activity and inhibitory effect on osteoclast production in vitro, that was reflected in vivo. It blocked MET and VEGFR2 phosphorylation in prostate cancer cells and osteoblast-like cells, respectively. Conclusion: These data indicate that cabozantinib has direct anti-tumor activity; and that its ability to modulate osteoblast activity may contribute to its anti-tumor efficacy.”
Tokito T, Shukuya T, Akamatsu H, Taira T, et al. Cancer Chemother Pharmacol. Mar 27, 2013.
“Skeletal-related events (SREs) negatively affect the quality of life of patients with cancer. Vascular endothelial growth factor receptor (VEGFR)-targeted therapy is effective against bone metastasis in animal models, but the clinical efficacy of anti-VEGFR inhibitors against bone metastases remains unclear. Therefore, we aimed to investigate the efficacy of chemotherapy with bevacizumab, an anti-VEGF antibody, against bone metastases.”