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• W2087987208 abstract "Abstract Background: Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins, can lead to cancer cell death. Ganetespib (G) is a 2nd generation Hsp90 inhibitor (Hsp90i) that has single agent clinical activity in patients with ALK, KRAS, HER2, and BRAF mutations. G also inhibits pathways implicated in resistance to taxanes, including hypoxia pathways (HIF-1α) as well as cell-cycle and DNA repair pathways. Combination of G with docetaxel (D) has shown synergy in NSCLC xenografts and prolongation of progression-free survival (PFS) and overall survival (OS) of patients with NSCLC adenocarcinoma in interim analyses of the GALAXY-1 trial. Methods: Patients enrolled in GALAXY-1 (n=253) receive D 75 mg/m2 on D1 of a 3-week treatment cycle; combination arm patients receive G 150 mg/m2 on D1 and D15 in addition. The co-primary endpoints are PFS in patients with elevated baseline level of serum LDH and PFS in the mutant KRAS population. PFS and OS in all adenocarcinoma patients are key secondary endpoints. Genomic profiling using Affymetrix Oncoscan™ was performed on archival tissues obtained at baseline, with the goal of determining biomarkers predictive of ganetespib activity Results: Tumor tissue samples from 65 patients and 26 matched normal tissues were processed on the Affymetrix OncoScan™ FFPE Express 2.0 Services assay. The OncoScan™ FFPE Express 2.0 assay contains 332941 copy number probes. After removing samples with average call rates lower than 90%, 296522 markers on chromosome 1-22 were selected for copy number analyses. For preliminary evaluation of interactions between copy number aberrations and treatment response in the G arm, a genome scale Kaplan-Meier Estimates PFS analysis at each of 296522 markers was performed. Conclusions: Genomic profiling using OncoScan™ is utilized in the GALAXY-1 trial to identify biomarkers of response/resistance to ganetespib administered in combination with docetaxel. Complete analyses will be presented at the meeting. Note: This abstract was not presented at the meeting. Citation Format: Dean Fennell, Alexey Antonov, Miguel L. Martins, Sanjay Popat, Suresh S. Ramalingam, James Spicer, Vojislav M. Vukovic, Iman El-Hariry, Vienna Reichert, Rafael Rosell. Evaluation of genomic profiling in the GALAXY-1 (NCT01348126), a randomized Phase 2b study of ganetespib in combination with docetaxel versus docetaxel alone as second line therapy in patients with advanced NSCLC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4657. doi:10.1158/1538-7445.AM2014-4657" @default.
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• W2087987208 title "Abstract 4657: Evaluation of genomic profiling in the GALAXY-1 (NCT01348126), a randomized Phase 2b study of ganetespib in combination with docetaxel versus docetaxel alone as second line therapy in patients with advanced NSCLC" @default.
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