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CTIX -- Cellceutix Corporation
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[QUOTE]Originally posted by BooDog: [QB] Cellceutix at ASCO 2015 A phase 1, dose-escalation, safety, pharmacokinetic, pharmacodynamic study of thioureidobutyronitrile, a novel p53 targeted therapy, in patients with advanced solid tumors. Sub-category: Cytotoxic and Other Novel Agents Category: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics Meeting: 2015 ASCO Annual Meeting Abstract No: TPS2613 Poster Board Number: Board #323a Citation: J Clin Oncol 33:5s, 2015 (suppl; abstr TPS2613) Author s Geoffrey Shapiro, James Walter Mier, John Frederick Hilton, Leena Gandhi, Nicole G. Chau, Andrea J. Bullock, Jeffrey G Supko, Sigitas Jonas Verselis, Kayla Murgo, Cameron Sze, Susan Gotthardt, Andrew Wolanski, W. James Alexander, Ashok Kumar, Sylvia Adell Holden, Karima Chafai-Fadela, Siya Ram, Krishna E. Menon; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Dana-Farber/Harvard Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA; Cellceutix Corporation, Beverly, MA; Cellceutix Corp, Beverly, MA; Cellceutix, Beverly, MA Abstract Disclosures Abstract: Background: Thioureidobutyronitrile, Kevetrin, induced apoptosis in wild type p53, mutant p53 and p53 null cell lines. In A549 lung carcinoma cells, wild type p53 was stabilized by Kevetrin. Kevetrin induced nongenotoxic activation of the p53 signaling pathway. Kevetrin also induced p21 and PUMA, known transcriptional targets of p53. Kevetrin caused accumulation of monoubiquitinated p53 and induced transcriptional independent apoptosis. In p53 mutant breast carcinoma cells (MDA-MB-231), Kevetrin induced degradation of hyperstable oncogenic mutant p53 and induced apoptotic cell death. Apoptotic cell death was also induced in K-562, a p53 null CML cell line. Consistent with in vitro data, Kevetrin showed potent antitumor activity in wild type p53 (A549), mutant p53 (MDA-MB-231), and p53 null (K-562) human tumor xenograft models. Kevetrin has the unique ability to target both wild type and mutant p53 tumors controlling tumor growth in various preclinical tumor models (ASCO 2013). Based on the pre-clinical data, a Phase I study was initiated at Dana-Farber/Harvard Cancer Center in 2012. Methods: Adults with refractory locally advanced or metastatic solid tumors, acceptable liver, kidney function, and hematologic status were eligible. Objectives include determination of DLT, MTD, pharmacokinetics, pharmacodynamics, and evaluating preliminary evidence of antitumor activity. Kevetrin is given as an intravenous infusion once weekly for 3 weeks in 28-day cycles. The starting dose was 10 mg/m2. In a 3+3 design, groups of 3-6 patients are evaluated for toxicity at each dose level. Dose escalation is based upon the number and intensity of adverse events in cycle 1. Kevetrin PK is characterized for the first and last doses given in cycle 1. Kevetrin induced p21 in lymphocytes preclinically; therefore p21 expression in peripheral blood mononuclear cells is measured as a PD biomarker. Antitumor activity by RECIST 1.1 criteria and serum tumor markers is assessed. The p53 status of tumors of selected patients will be determined. The first nine cohorts were completed in December 2014. Enrollment in the tenth cohort at 450 mg/m2 began January 2015. Clinical trial information: NCT01664000 http://abstracts.asco.org/156/AbstView_156_149817.html https://clinicaltrials.gov/show/NCT01664000 as well for reference. CTIX has also moved on to the 11th cohort [URL=http://cellceutix.com/cellceutix-reports-results-for-quarter-ended-march-31-2015-enrollment-for-oral-mucositis-studies-to-begin-this-month/#sthash.k1mZ6uL6.dpbs]http://cellceutix.com/cellceutix-reports-results-for-quarter-ended-march-31-2015 -enrollment-for-oral-mucositis-studies-to-begin-this-month/#sthash.k1mZ6uL6.dpbs [/URL] [/QB][/QUOTE]
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