A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1).

CRA8007 Background: Heat shock protein 90 chaperone function is critical for the biological effects of several oncoproteins. Ganetespib (G) is a highly potent 2nd-generation Hsp90 inhibitor with a favorable safety profile and single-agent clinical activity. Methods: Based on synergistic preclinical interactions between docetaxel (D) and G, we conducted a randomized (1:1), international open-label study of D with or without G. Patients with advanced lung adenocarcinoma, one prior systemic therapy, and ECOG PS 0/1 were included. D was given at 75 mg/m2 on day 1 of a three-week cycle. In the experimental arm, D was given on day 1 and G at 150 mg/m2 on days 1 and 15. The co-primary endpoints were PFS in patients with elevated LDH (eLDH) levels, or tumors harboring KRAS mutations. Key secondary endpoints were OS and PFS in all adenocarcinoma patients. Target enrollment was 240 adenocarcinoma, 120 eLDH, and 80 mKRAS patients. Statistical tests are 1-sided. Results: Enrollment of 255 adenocarcinoma patients comp...