MethylGene Presents MGCD265 Data at the 24th European Organization for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics
Published: Nov 08, 2012
In the poster entitled “A Novel Assay for the Met Inhibitory Activity of MGCD265 in Plasma From Solid Tumor Patients in a Dose Escalating Phase I Study” data was presented using an ex vivo assay, in which plasma samples from patients treated with MGCD265 were tested for the ability to inhibit Met phosphorylation in a human cancer cell line. In the ongoing clinical trials, patient plasma levels have been reached that result in ~80% inhibition of Met phosphorylation. In companion studies using a human tumor xenograft model, Met inhibitory activity in mouse plasma correlated with inhibition of Met phosphorylation in the tumor as well as dose-dependent inhibition of tumor growth.
“It is encouraging that the MGCD265 exposures in patients and the accompanying level of Met inhibition are in the range at which tumor growth inhibition is observed in animal models.” said Dr. Jeffrey Besterman, Chief Scientific Officer of MethylGene.
MGCD265, a rationally designed, orally administered small molecule kinase inhibitor designed to target Met and the VEGFR 1,2, and 3 receptor tyrosine kinases (RTKs). RTKs, including Met, are key kinases involved in cancer, angiogenesis (a process whereby new blood vessels are formed to nourish the tumors), tumor cell metastasis, tumor development and survival. Met expression is elevated and associated with tumorigenesis in several solid tumor indications including NSCLC, gastric, prostate, colorectal, bladder, breast and ovarian cancers. Phase I/II studies of single agent MGCD265 and combinations with erlotinib or docetaxel are currently underway.
More than 200 patients have been treated to date in clinical studies of both single-agent and combination therapy with docetaxel or erlotinib. In combination trials, six of 104 patients have been on study for over one year at a variety of doses: NSCLC (n=2), GE cancer (n=2), ovarian cancer (n=1) and chordoma (n=1). Additionally, disease control in the combination study was observed in 11/12 NSCLC patients (with two partial responses) and 4/9 patients with GE cancer (2 non-complete response/non-progressive disease). MGCD265 continues to demonstrate a favorable safety profile. Drug-related diarrhea, fatigue and lipase elevation have been observed in patients receiving MGCD265 monotherapy The maximum tolerated dose has not yet been defined and dose escalation continues.
MethylGene Inc. (TSX:MYG) is a drug development company that is advancing novel therapeutics for the treatment of human diseases including cancer and infectious disease. The Company’s lead product candidates are: MGCD290, an oral antifungal agent targeting the fungal Hos2 enzyme that is in Phase II trials for vulvovaginal candidiasis, and MGCD265, an oral Met/VEGF receptor kinase inhibitor that is in Phase I/II clinical trials for solid tumor cancers. MethylGene owns all rights to its lead product candidates, and has partnerships with Otsuka Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and EnVivo Pharmaceuticals, Inc. for its other pipeline programs.
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