The phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer, and whose tumors had PTEN loss.
In this patient group, ipatasertib in combination with abiraterone and prednisone/prednisolone provided a statistically significant reduction in the risk of disease worsening or death, compared to current standard of care (abiraterone and prednisone/prednisolone) plus placebo. The other co-primary endpoint of rPFS in the overall study population (intention-to-treat) was not met.
The trial is funded by Genentech, a member of the Roche Group.The safety profile for the combination of ipatasertib and abiraterone was consistent with previous analyses and known risks.
Overall survival benefit and additional secondary endpoints are not yet mature. The trial will continue until the next planned analysis and data will be shared with health authorities.
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signaling pathway—a key driver of cancer cell growth and proliferation in prostate cancer. The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as androgen receptor inhibition is associated with an increase in AKT pathway activation.
Functional loss of the tumor suppressor protein PTEN within the tumor, seen in approximately 40-60% of mCRPC patients, results in hyperactivation of the PI3K/AKT pathway and is associated with adverse outcomes such as increased tumor grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.
Genentech’s clinical development program for ipatasertib focuses on tumors that are frequently found to have activation of the PI3K/AKT pathway. In addition to prostate cancer, ipatasertib is being studied in certain types of breast cancer including triple-negative breast cancer (TNBC) and hormone-receptor positive (HR+), HER2- negative breast cancer. Results are anticipated later in 2020.
