LEXINGTON, Mass.--(BUSINESS WIRE)--

Synta Pharmaceuticals Corp. (SNTA) today announced encouraging results from a planned interim analysis of the GALAXY trial, a randomized Phase 2b/3 study designed to evaluate the efficacy and safety of the Companys lead Hsp90 inhibitor, ganetespib, in combination with standard-of-care docetaxel vs. docetaxel alone as second-line treatment for advanced non-small cell lung cancer (NSCLC).

The GALAXY trial is based on a two-stage, operationally adaptive design. The first-stage, randomized, open-label, 240-patient Phase 2b portion of the trial is designed to enroll Stage IIIB/IV NSCLC patients who have progressed following one prior line of therapy, with the goal of determining biomarkers predictive of ganetespib activity. Results will be used to guide choice of patient population for the Phase 3 stage of the trial.

Patients in the GALAXY trial are randomized 1:1 to receive ganetespib plus docetaxel or docetaxel alone. Patients in both arms receive a standard regimen of docetaxel 75 mg/m2 on day 1 of a 21-day cycle; patients in the combination arm receive in addition ganetespib 150 mg/m2 on days 1 and 15. Treatment continues until disease progression per RECIST 1.1 criteria.

The co-primary endpoints of GALAXY are PFS (progression-free survival) in patients with elevated baseline level of serum LDH (lactate dehydrogenase), and PFS in the mutant KRAS population. PFS and OS (overall survival) in all adenocarcinoma patients are key secondary endpoints. Serum LDH levels and tumor KRAS mutation status are assessed by independent central laboratories.

Elevated LDH: Elevated baseline LDH occurs in approximately one quarter to one third of advanced cancer patients in clinical trials and is prognostic of poor clinical outcomes in many cancer types, including lung cancer.[1-3] While elevated LDH can result from several conditions, in cancer patients elevated levels of LDH and its isoforms have been associated with tumor hypoxia (lack of oxygen).[4,5] Inhibition of hypoxia pathways has been shown to enhance anti-cancer activity of taxanes and other chemotherapies.[6] Recent results from trials evaluating agents that target hypoxia-related pathways, including VEGF and mTOR inhibitors, have shown correlation between elevated LDH and improved clinical activity.[7-10] In laboratory experiments, treatment with ganetespib potently suppresses HIF-1alpha, a critical regulator of hypoxic pathways[11] supporting potential application for ganetespib in combination with taxanes in this patient population.

KRAS mutation: Activating KRAS mutations, estimated to occur in 15-30% of NSCLC patients, are also associated with poor clinical outcomes and limited therapeutic options.[12,13] Hsp90 is required for the proper function of a number of key signaling proteins in the KRAS pathway, while inhibition of Hsp90 by ganetespib has shown promising activity in laboratory models of this disease.[14] Recent results from trials evaluating ganetespib monotherapy in lung, colon, and gastric cancers have further suggested promising potential in patients with KRAS mutations.

Based on a target enrollment of 240 adenocarcinoma patients, GALAXY is 90% powered to detect a PFS improvement from 6 to 12 weeks in elevated LDH patients and from 5 weeks to 10 weeks in the mutant KRAS patients. For the key secondary endpoints: in all adenocarcinoma patients, GALAXY is 88% powered to detect an improvement in PFS from 3 to 4.5 months, and 73% powered to detect an improvement in OS from 6 to 8.5 months. All powering assumptions are based on a 1-sided alpha of 0.05. An interim analysis was planned when approximately 50% of patients had been enrolled and had sufficient follow up, defined as one post-baseline scan.

GALAXY Interim Results

At the time of this interim analysis, a total of 114 adenocarcinoma and 69 non-adenocarcinoma patients had been enrolled. Following a review earlier this year that determined low likelihood of benefit in the non-adenocarcinoma population, the trial was modified to enroll only adenocarcinoma patients. Results reported below are for adenocarcinoma patients only.

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Synta Announces Results from Interim Analysis of the Randomized Phase 2b/3 GALAXY Trial Evaluating Ganetespib plus ...