Synta Pharmaceuticals (SNTA) has released promising results from a randomised, multi-centre GALAXY-1 trial of its lead drug candidate, the Hsp90 inhibitor ganetespib in combination with docetaxel versus docetaxel alone for treatment of patients with non-small cell lung adenocarcinoma (NSCLC) tumours.
So far, around 800 patients were treated with ganetespib in more than 25 clinical trials, which demonstrated durable objective responses, including CRs (complete responses) and near-CRs, when used alone, as monotherapy administration, in patients with several different types of late-stage cancer.
The drug candidate has also shown favourable safety profile, with no evidence of the serious liver or common ocular toxicities seen with other Hsp90 inhibitors.
Synta president and CEO Safi Bahcall said the company's strategy with the GALAXY lung cancer programme has been to use a large, global Phase IIb trial to increase the probability of a positive outcome in Phase III.
"We designed the GALAXY-1 trial, which enrolled close to 400 patients in total, to address two primary questions: One: How to optimise patient selection for Phase 3, and two: how to reduce the operational risks from heterogeneous populations and treatment patterns that often confound large, pivotal studies," Bahcall said.
"The one-year follow-up results from GALAXY-1 address both these questions, confirming our choices for patient selection and increasing our confidence in a positive outcome for the ongoing GALAXY-2 trial."
Major findings of the GALAXY-1 trial include 65% of overall survival (OS) events in the primary adenocarcinoma population, with about 70% of OS events targeted for final analysis by early 2014.
The positive one-year follow-up results also showed improvements in OS in the prespecified chemosensitive patient population, together with a lack of activity in the refractory population, which confirmed the selection of the chemosensitive patient population for the GALAXY-2 Phase III trial.
OS hazard ratio in the chemosensitive population was 0.75 and 0.72 in the Cox proportional hazards univariate (unadjusted) and multivariate (adjusted) models, respectively, while median overall survival was 10.7 months for ganetespib and docetaxel versus 7.4 months for docetaxel alone.
Consistent with prior findings with ganetespib, reports of visual impairment in this study were infrequent: 2% in the G+D arm and 0% in the D arm.
The GALAXY-1 trial is also assessing two other potential biomarkers, elevated LDH (eLDH) and mutant KRAS (mKRAS), for use in selecting patients for the Phase III trial.
According to the results from preclinical studies carried out by Synta collaborators at the University of Leicester in the UK, intact mitochondrial signaling pathways are required for ganetespib to induce cancer cell death.
Preclinical results showed that ganetespib reduced tumour invasiveness, including the ability of tumours to spread (metastasis) and grow new blood vessels (angiogenesis).
These results are consistent with GALAXY-1 findings: the appearance of new lesions was substantially reduced in the ganetespib arm as compared with the control arm.
Ganetespib is administered through intravenous route and a synthetic, small-molecule inhibitor of heat shock protein 90.
The drug previously received fast-track designation from the FDA for second-line treatment of non-small cell lung adenocarcinoma in combination with docetaxel.
Image: Micrograph of squamous carcinoma, a type of non-small cell lung adenocarcinoma (NSCLC). Photo: courtesy of Nephron.