Adding ipatasertib to standard treatment for metastatic castration-resistant prostate cancer (mCRPC) significantly extended survival without disease worsening in a group of men whose tumors lack the PTEN protein, a Phase 3 clinical trial found.

But the combination, which included ipatasertib plus standard Zytiga (abiraterone acetate) and prednisone/prednisolone, failed to extend the time without disease progression or death in the overall mCRPC population, the researchers noted.

“The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer,” Levi Garraway, MD, PhD, chief medical officer and head of global product development, said in a press release.

Ipatasertib, developed by Genentech, is an oral investigational medicine that works by binding and blocking the AKT proteins, which are key drivers of cancer cell growth and proliferation in prostate cancer.

Increased AKT activity also has been implicated in resistance to anti-androgen therapy, which aims to deprive prostate cancer cells of androgens like testosterone, their primary fuel for growth.

This signaling pathway also is overactive in patients whose tumors lack PTEN, a tumor suppressor protein that works to prevent cancer formation. PTEN is lost in about 40–60% of mCRPC patients and this often is associated with worse outcomes, such as more advanced cancer, earlier recurrence after surgery, metastasis, and cancer-specific death.

Zytiga is a second-generation androgen receptor inhibitor developed by Janssen Oncology, that works by blocking the signaling of androgens that fuel prostate cancer growth.

The IPATential150 Phase 3 trial (NCT03072238) is assessing the safety and efficacy of ipatasertib, given alongside the standard androgen receptor inhibitor Zytiga and a corticosteroid (prednisone or prednisolone), in mCRPC patients whose cancer is asymptomatic or mildly asymptomatic. 

The double-blind trial enrolled 1,101 patients and assigned them randomly to receive ipatasertib plus standard Zytiga and prednisone/prednisolone, or placebo plus standard treatment. All medicines were taken daily by mouth, and treatment was continued until patients experienced signs of disease progression or unacceptable toxicity.

IPATential150’s main goal was to determine if the ipatasertib combo was better than standard treatment at extending survival without prostate cancer progression on imaging scans — a measure defined as radiographic progression-free survival (rPFS) — both in the overall population and in patients with PTEN loss.

Secondary measures include time to worsening of pain, time to needing chemotherapy, time to deterioration in function, proportion of patients experiencing a drop in tumor size after treatment, and overall survival.

The trial met one of its co-primary goals, with the combination of ipatasertib plus Zytiga and prednisone/prednisolone significantly extending rPFS in mCRPC patients lacking the PTEN protein.

But the other co-primary goal of extending rPFS in the overall population was not met, suggesting that the ipatasertib combo does not work as well in patients with a functional PTEN protein.

While the safety profile for the ipatasertib combo was consistent with the known safety profile of each agent alone, the data for other secondary goals was not yet mature. The trial will continue until the next planned analysis and the company is planning to present the data at an upcoming medical conference.

In addition to prostate cancer, ipatasertib also is being studied in breast and gastric cancer.