New trials - general information

[Guest guest]

There are currently 11 trials for CML at MDACC. I researched the following, as

they are newer ones:

INNO-406 (formerly known as NS-187) is a potent, oral, rationally designed, dual

Bcr-Abl and Lyn-kinase inhibitor currently in Phase I clinical studies.

According to a study published in the journal Blood (Dec. 1, 2005), INNO-406 is

25 to 55 times more potent than imatinib in vitro, and at least 10 times as

effective as imatinib mesylate in suppressing the growth of Bcr-Abl bearing

tumors. INNO-406 has demonstrated activity in 12 of 13 imatinib-resistant cell

lines. In addition to its Bcr-Abl inhibitory properties, INNO-406 inhibits Lyn

kinase. Upregulation of Lyn kinase activity is a well-recognized cause of

imatinib resistance. Lyn kinase activation has also been documented in a variety

of solid tumors, including prostate cancer.

http://www.redorbit.com/news/health/903792/innovive_pharmaceuticals_announces_in\

terim_phase_i_data_on_inno406_for/index.html?source=r_health____________________\

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CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq:

VRTX - News) and Merck & Co., Inc. today provided an update to their

collaborative Aurora kinase research and development program, which is targeting

the treatment of cancer. Merck has suspended enrollment in clinical trials of

the lead investigational Aurora kinase inhibitor in the collaboration, MK-0457

(VX-680), pending a full analysis of all efficacy and safety data for MK-0457.

The decision was based on preliminary safety data, in which a clinical safety

finding of QTc prolongation was observed in one patient.

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Seventeen subjects have received at least one dose of XL228, of whom 16 had

completed Cycle 1 as of May 15, 2008. The trial is evaluating a treatment cycle

consisting of 4 weekly 1-hour IV infusions of XL228 at doses ranging from 0.45

mg/kg to 7.2 mg/kg. Thirteen of the 17 subjects (76.5%) have BCR-ABL mutations,

including seven (41.2%) with the T315I mutation. At the 3.6 and 7.2 mg/kg doses

(either as part of Cohorts 4 and 5 or through dose escalation from a previous

cohort), all subjects have demonstrated stable or decreasing white blood cell

counts.

" The data presented today provide evidence that XL228 inhibits wild type and

clinically relevant mutant forms of BCR-ABL at well tolerated doses, " said

M. sey, PhD, President of Research and Development at Exelixis.

" To date, all patients dosed at or above 3.6 mg/kg have experienced decreases in

leukocytes, and/or decreased use of hydroxyurea resulting in prolonged stable

disease. Importantly, initial signs of clinical activity have been observed in

patients with mutant forms of BCR-ABL, including the imatinib-, dasatinib-, and

nilotinib-resistant BCR-ABL mutant T315I. These data suggest that XL228 may have

important clinical utility for patients with CML or Ph+ALL, including those

resistant or intolerant to current therapeutics. "

http://www.globeinvestor.com/servlet/story/PRNEWS.20080613.AQF509/GIStory/

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PHA-739358

A small-molecule 3-aminopyrazole derivative with potential antineoplastic

activity. Aurora kinase inhibitor PHA-739358 binds to and inhibits the Aurora

kinases, which may result in cell growth arrest and apoptosis in tumor cells in

which Aurora kinases are overexpressed. This agent may preferentially bind to

and inhibit Aurora B kinase. Aurora kinases, a family of serine-threonine

kinases, are important regulators of cellular proliferation and division. Check

for active clinical trials or closed clinical trials using this agent. (NCI

Thesaurus) http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=489092

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SGX 393 - This drug candidate could build on the legacy of Gleevec, which has

been the gold standard for treating this leukemia and was developed by

Druker, M.D., director of the OHSU Cancer Institute. Despite Gleevec’s success,

some CML patients develop resistance to Gleevec, often due to mutations that

interfere with drug binding.

This drug candidate could build on the legacy of Gleevec, which has been the

gold standard for treating this leukemia and was developed by Druker,

M.D., director of the OHSU Cancer Institute.

http://www.cancercommentary.com/2007/12/27/sgx393-new-drug-candidate-that-knocks\

-out-resistant-form-of-chronic-myeloid-leukemia-cml/

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ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that clinical

investigators from leading cancer centers will present Phase 2 and 1b clinical

data from ongoing trials of the Company's novel mTOR inhibitor, AP23573, at the

annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago,

Illinois, on Sunday, June 3, 2007. Additional data from the Phase 2 trial of

single-agent AP23573 in patients with soft-tissue and bone sarcomas and initial

results from the Phase 2 trial of single-agent AP23573 in progressive

endometrial cancer will be presented.

http://www.drugs.com/clinical_trials/clinical-data-ariad-s-novel-mtor-inhibitor-\

ap23573-presented-asco-annual-meeting-1025.html

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Blessings,

Lottie