Roche phase 3 hits goal in subgroup of prostate cancer patients

Roche’s ipatasertib has improved progression-free survival (PFS) in a subgroup of prostate cancer patients in a phase 3 trial. The drug failed to improve outcomes in the broader population, but, with overall survival data still maturing, Roche thinks the findings are encouraging for its chances of claiming a slice of a market targeted by AstraZeneca.

Ipatasertib is designed to treat tumors by inhibiting the PI3K/AKT signaling pathway. The approach is potentially particularly relevant to cancers in which AKT becomes hyperactivated, for example due to the inactivation of a tumor suppressor gene, and drives tumorigenesis. However, efforts to drug AKT have generated lackluster results, with GlaxoSmithKline pulling the plug on GSK690693 amid safety concerns and Merck’s MK-2206 failing on efficacy.

The failure of other AKT inhibitors has made ipatasertib a front-runner in the field. Friday, Roche and its Genentech subsidiary shared top-line findings from a phase 3 trial that could dictate whether they can capitalize on ipatasertib’s position at the front of the pack by bringing the drug to market.

Roche designed the trial primarily to assess whether giving ipatasertib in combination with Johnson & Johnson’s Zytiga improves PFS in patients with metastatic castrate-resistant prostate cancer. The trial generated mixed results against that primary endpoint.

Across the entire 1,101-subject study, the combination was statistically no better than Zytiga alone. However, adding ipatasertib to Zytiga improved PFS in a prespecified analysis of a subpopulation of patients with PTEN-loss tumors. PTEN is one of the tumor suppressor genes that, when inactivated, is associated with hyperactivation of AKT.

Roche is yet to share full data from the trial, but the top-line findings suggest ipatasertib may have a future. There is a mechanistic explanation for why ipatasertib would perform better in patients with PTEN-loss tumors. And as PTEN loss happens in around half of metastatic castrate-resistant prostate cancer patients, the subpopulation is large enough to be a commercially viable opportunity. 

A clearer picture of whether Roche can seize that opportunity will start to emerge as the Swiss Big Pharma releases data from the trial. Roche plans to share a look at the results gathered to date at an upcoming medical meeting. At some point, Roche will also get the mature overall survival data it needs to show whether ipatasertib improves that key secondary endpoint.

Roche will work to gather those results while also advancing ipatasertib in breast cancer. Three phase 3 trials of ipatasertib in different subpopulations and treatment combinations are underway, setting Roche up to generate data for a possible showdown with AstraZeneca’s capivasertib. AstraZeneca is testing its rival AKT inhibitor in two phase 3 breast cancer trials but is yet to advance past phase 1 in prostate cancer.