Background: Hsp90 is a molecular chaperone recognized as a key facilitator of cancer cell growth and survival. Ganetespib is a resorcinolic Hsp90 inhibitor that has shown single-agent activity in patients with lung, breast, and other cancers after progression on standard treatments. Ganetespib in combination with docetaxel induces synergistic efficacy in human non-small-cell lung carcinoma (NSCLC) tumor xenografts. Ganetespib is well tolerated and has not shown severe liver or common ocular toxicities reported for other Hsp90 inhibitors. Transient diarrhea is the most common adverse event, and is manageable with appropriate supportive care. A large randomized study of ganetespib in combination with docetaxel in advanced NSCLC patients (GALAXY-1 Trial) is ongoing. Preliminary results indicate good tolerability of the combination, and improvement in efficacy, including OS. Methods: GALAXY-2 is a randomized (1:1), international, open-label phase III study enrolling patients who received and progressed on one prior systemic therapy for advanced NSCLC of adenocarcinoma histology. Patients (N=500) are prospectively stratified for ECOG PS, total LDH, and best response to first-line therapy. The primary endpoint is OS. Key secondary endpoints include: OS in 3 subpopulations (mKRAS and elevated LDH and LDH5); PFS, ORR, DCR, DOT, and DOR. Patients in the control arm are treated with docetaxel 75 mg/m² on Day 1 of a 3-week cycle. In the combination arm, ganetespib 150 mg/m² is given on Day 1 with 75 mg/m² docetaxel, and ganetespib 150 mg/m² alone is given on Day 15 of each 3-week cycle. Two interim analyses for OS will be performed. Tumor tissue and blood samples will be collected for planned translational studies.