Synta Pharmaceuticals Corp.,a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs, has treated first patient in the randomized GALAXY-2 phase III trial designed to evaluate docetaxel plus ganetespib, its investigational Hsp90 inhibitor, versus docetaxel alone for the second-line treatment of non-small cell lung adenocarcinoma. The study will enroll approximately 500 patients from about 140 cancer treatment centers worldwide.
“The clinical results presented from the GALAXY-1 trial so far have been encouraging,” said Vojo Vukovic, MD, chief medical officer of Synta. “The confirmatory GALAXY-2 trial is critical for delivering on our regulatory strategy in non-small cell lung cancer (NSCLC) and achieving our goal of bringing ganetespib to patients with this devastating disease.”
The GALAXY programme is based on a two-stage, operationally adaptive trial design, with the first phase IIb/III stage (GALAXY-1) intended to identify the optimal patient population to be evaluated in a confirmatory phase III trial (GALAXY-2). An interim analysis of adenocarcinoma patients in GALAXY-1 presented last September supported potential activity in the second-line treatment setting. The prespecified patient population in GALAXY-1 with a diagnosis of advanced disease more than six months prior to study entry, i.e., those patients who generally received a normal course of first-line chemotherapy before experiencing disease progression (approximately two-thirds of enrolled patients), was chosen for further evaluation in GALAXY-2.
GALAXY-2 will enroll approximately 500 patients with Stage IIIB/IV non-small cell lung adenocarcinoma who were diagnosed with advanced disease at least six months prior to study entry and received one prior chemotherapy-based regimen for metastatic disease. All patients must have documented disease progression and ECOG performance status of 0 or 1. Enrollment will be stratified to ensure the balance of key prognostic factors including ECOG performance status (0 versus 1), baseline level of LDH (greater versus less than upper limit of normal), and best response to first-line therapy (complete response or partial response versus stable disease or progressive disease). Patients will be randomized 1:1 to receive ganetespib plus docetaxel, or docetaxel alone, at the same dose and schedule as in the GALAXY-1 trial. Docetaxel will be administered at 75 mg/m2 on day 1 of a 21-day treatment cycle in both arms. Patients in the combination arm will also receive ganetespib 150 mg/m2 on days 1 and 15. In the combination arm, following the completion of docetaxel therapy, treatment with ganetespib alone may be continued until disease progression or treatment intolerance.
The primary endpoint of the GALAXY-2 trial is overall survival. Two event-driven interim analyses are planned, which will be reviewed by an independent data monitoring committee. Key secondary endpoints include progression-free survival and overall response rate, as well as overall survival in certain prespecified biomarker-defined subpopulations. Based on current projections, Synta expects the interim and final analyses of the GALAXY-2 trial to be conducted in 2014.
Ganetespib, an investigational drug candidate, is a selective inhibitor of heat shock protein 90 (Hsp90), a molecular chaperone which controls the folding and activation of a number of client proteins that drive tumor development and progression. Many solid and hematologic tumors are dependent on, or become “addicted” to, Hsp90 client proteins including AKT, ALK, BCR-ABL, BRCA1, CDK1, CHK1, EGFR, FAK, HER2, HIF1-alpha, IGF-1R, MEK, MET, PDGFR, VEGFR, and WEE1. In preclinical models, inhibition of Hsp90 by ganetespib results in the inactivation, destabilization, and eventual degradation of many of these cancer-promoting proteins. A number of Hsp90 client proteins are also involved in the resistance of cancer cells to other anti-cancer treatments including chemotherapy, targeted therapy, and radiotherapy, supporting potential for ganetespib use in combination therapy. Ganetespib is being evaluated in over 20 clinical trials including trials in lung, breast, colorectal, and hematologic malignancies.
The GALAXY (Ganetespib Assessment in Lung cAncer with docetaXel) programme consists of two randomized trials comparing the combination of ganetespib and docetaxel versus docetaxel alone in patients with Stage IIIB/IV non-small cell lung cancer (NSCLC) who have received one prior systemic therapy: a 300-patient phase IIb/III trial (GALAXY-1) to determine the patient population most likely to derive benefit from ganetespib, and a 500-patient confirmatory phase III trial (GALAXY-2).
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases.