The GALAXY Trial(NCT01348126): A randomized IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects with stage IIIB or IV NSCLC.

Abstract

TPS7613^ Background: Hsp90 is a molecular chaperone required for proper folding and activation of many cancer-promoting proteins and is recognized as a key facilitator of cancer cell growth and survival. In pre-clinical models, Hsp90 inhibition causes degradation of multiple client proteins and leads to cancer cell death. Ganetespib is a resorcinolic Hsp90 inhibitor that has shown potent anti-tumor activity in patients with lung, breast, and other cancers that had progressed on standard treatment agents. Moreover, combination of ganetespib with docetaxel results in synergistic antiproliferative effects in several human non-small cell lung carcinoma (NSCLC) tumor xenografts. Ganetespib is well tolerated and is devoid of severe liver or common ocular toxicities that have been observed with some other Hsp90 inhibitors. Diarrhea is the most common adverse event and is manageable with appropriate supportive care. In a recent report, ganetespib administered at 200 mg/m2 weekly showed activity in pretreated patients with advanced NSCLC patients with ELM4-ALK translocation and KRAS mutations. Methods: Stage 1 (240 subjects): randomized, international open-label Phase 2B study in subjects that progressed on or after one prior systemic therapy for stage IIIB or IV NSCLC: patients are prospectively stratified for ECOG performance status, histology, total LDH, interval since diagnosis, and smoking status. Co-primary endpoints are PFS in the ITT population, and PFS in patients with KRAS mutations. Main secondary endpoints include ORR, disease control rate, OS and clinical activity in different molecular subtypes, including BRAF, HER2, EGFR, EML4-ALK. Patients on the control arm are treated with docetaxel 75 mg/m2 on day 1 of a three-week cycle. In the combination arm, ganetespib 150 mg/m2 is given on day 1 (with docetaxel) and day 15 of a three-week cycle. At the time of submission 90 subjects had been enrolled in Stage 1.