Molecular Profiling as an Outcome Predictor in the Galaxy Trialtm (NCT01348126): A Randomized IIB/III Study of Ganetespib (STA-9090) in Combination with Docetaxel Versus Docetaxel Alone in Subjects with Stage IIIB/IV NSCLC

ABSTRACT Background Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins, can lead to cancer cell death. Ganetespib is an Hsp90 inhibitor that has shown single agent activity in molecularly defined disease, including ELM4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. The AS/RAF/MEK/ERK pathway is a potential therapeutic target in non-small cell lung cancer (NSCLC). Methods This randomized trial compares ganetespib (G) + docetaxel (D) to D in 2nd line advanced NSCLC patients. Archival tissue collection was mandatory and included formalin-fixed paraffin-embedded (FFPE) 10 unstained slides at 5 or 10 um and 1 matching hematoxylin-eosin (HE)-stained slide. The aim of this study is to investigate the predictive value of most commonly occurring known mutations in NSCLC in association with the efficacy of G + D, including KRAS, EGFR, BRCA, MET, BRAF and others. Genetic mutational analysis was analyzed using Affymetrix OncoScan™ FFPE Express platform, which provides information on copy number variation, allele ration and somatic mutations, Additionally, KRAS mutations were also analyzed separately using real-time PCR based sequencing. Results are correlated with baseline demographics and efficacy outcome data. Results Approximately 160 of the 300 planned patients were enrolled by early May. Median age was 60 yrs (range 39-86), M/F: 105/53; adeno/other: 91/67; never/former/current smokers: 30/77/51. KRAS mutation was detected in 21 of first 140 patients (15%). Full genetic profiling is ongoing, and will be correlated with the efficacy outcomes from a planned interim analysis in early September, including disease control rate, PFS, and OS. Disclosure I. El Hariry: stock ownership. V. Vukovic: Stock options. F. Teofilovici: stock options. V. Reichert: stock options. All other authors have declared no conflicts of interest.