With fast-track status in hand for prostate cancer and two late-stage trials under way, OncoGenex Pharmaceuticals Inc.'s custirsen entered another Phase III study, this one in patients with non-small-cell lung cancer (NSCLC) whose disease has progressed despite chemotherapy.

An inhibitor of the cell-survival protein clusterin, the compound is partnered worldwide with Jerusalem-based Teva Pharmaceutical Industries Ltd., which is comparing survival in patients given custirsen combined with the standard NSCLC chemo agent docetaxel vs. docetaxel alone.

Called ENSPIRIT, the trial includes two formal interim analyses to find out if the trial should be stopped because of inadequate clinical benefit, but no early peeks will be made to determine efficacy.

In castrate-resistant prostate cancer, the Phase III study called SYNERGY is expected to complete enrollment later this year.

That trial is evaluating survival benefit in a first-line setting. SYNERGY is modeled after a Phase II trial that yielded a 6.9 month survival benefit (23.8 vs. 16.9 months) when added to docetaxel (and prednisone).

OncoGenex, of Bothell, Wash., recently disclosed the start of AFFINITY, a Phase III study that pairs custirsen, which is based on Carlsbad, Calif.-based Isis Pharmaceuticals Inc.'s second-generation antisense technology, with Jevtana (cabazitaxel), Paris-based Sanofi-Aventis SA's second-line therapy for prostate cancer.

Although antisense has had a rocky history, researchers find OncoGenex's approach promising because of the link between clusterin or prostate-specific antigen in the blood and circulating tumor cells, noted Leerink Swann analyst Jonathan Eckard, when his firm initiated coverage of the company in the spring.

"Any Phase III outcome even approaching the Phase II results [in prostate cancer] could validate both the target and drug," Eckard wrote in a research note.

OncoGenex also has OGX-427, an antisense heat shock protein 27 inhibitor, and reported Phase II results at the American Society of Clinical Oncology meeting in June.

Results showed a higher number of prostate cancer patients taking OGX-427 plus prednisone without disease progression at 12 weeks (71 percent), compared with those taking prednisone alone (40 percent).

HSP-27 expression is recognized in various cancers, Eckard pointed out, but "prior industry failures to target this multifunctional protein have deemed it 'un-druggable.'" OncoGenex owns worldwide rights to OGX-427.

While Teva is funding development and commercialization of custirsen, with a royalty plan for OncoGenex in the high-teens to mid-20s, OncoGenex retains all rights to OGX-427.