“The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer.”
Treatment with ipatasertib in combination with abiraterone acetate (Zytiga) and prednisone/prednisolone led to a statistically significant reduction in the risk of disease worsening or death compared with abiraterone and prednisone/prednisolone alone in patients with metastatic castration-resistant prostate cancer (mCRPC) and PTEN loss, according to initial findings released from the phase 3 IPATential150 trial.
This signified that 1 of the co-primary end points of the trial, radiographic progression-free survival (rPFS), had been met, Roche announced in a press release.
However, the other co-primary study end point of rPFS in the overall intent-to-treat population was not met.
“Prostate cancer remains a leading cause of death in men worldwide and patients with metastatic castration-resistant prostate cancer can be difficult to treat,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development, in a statement. “The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer.”
Overall survival and other secondary end points are continuing to be analyzed as data mature, and so the study will continue through the next planned analysis. These findings will be shared with health authorities and will be presented at an upcoming medical meeting.
Safety for the combination of ipatasertib and abiraterone was consistent with prior analyses of the agents and known risks.
Ipatasertib is an oral agent that targets and binds to the 3 isoforms of AKT, which blocks the PI3K/AKT signaling pathway. Loss of the tumor suppressor protein PTEN results in hyperactivation of the PI3K/AKT pathway and is associated with poor outcomes in patients with mCRPC.
The IPATential150 trial is a double-blind, placebo-controlled, multicenter, randomized phase 3 trial exploring the use of ipatasertib in combination with abiraterone acetate and prednisone/prednisolone for the treatment of adult male patients with asymptomatic or mildly symptomatic previously untreated mCRPC (NCT03072238). A total of 1101 patients were enrolled, including 521 patients with PTEN loss.
In the investigational arm, oral ipatasertib was given at 400 mg once daily continuously starting on day 1 of cycle 1 in combination with oral abiraterone tablets of 1000 mg daily plus 5 mg prednisone/prednisolone twice daily until disease progression or intolerable toxicity. Abiraterone was administered on an empty stomach and swallowed whole with water.
The primary end point was rPFS per Prostate Cancer Working Group 3 criteria in both the overall intention-to-treat and PTEN loss populations. Secondary end points included time to pain progression, time to initiation of cytotoxic chemotherapy, overall survival, time to function deterioration, time to prostate-specific antigen (PSA) progression, time to first opioid use, time to symptomatic skeletal event, objective response rate, PSA response rate, and plasma concentrations.
Patients were eligible to enroll if they had adequate hematologic and organ function, a life expectancy of at least 6 months, and willingness to track outcomes. An extension cohort was also open in the People’s Republic of China. All patients underwent PTEN immunohistochemistry testing using the Ventana (SP218) assay and were receiving ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analog or bilateral orchiectomy within 28 days of initiating treatment on the trial.
Those who had a history of liver disease, active infections requiring antibiotics, immunocompromised status, or a history of ventricular dysrhythmias or other malignancies or diseases were excluded from participating in the trial. Other exclusion criteria included prior treatment with abiraterone, enzalutamide (Xtandi), flutamide, bicalutamide, 5-alpha reductase inhibitors, systemic radiopharmaceuticals, or other experimental therapies targeting the PI3K pathway. Patients with uncontrolled hypertension, pituitary or adrenal dysfunction, cardiac arrhythmias, inflammatory bowel disease, or type 1 or 2 diabetes were also excluded.
Ipatasertib is also being investigated in trials of tumors that show frequent activation of the PI3K/AKT pathway, including prostate and breast cancers.
Roche’s IPATential150 study evaluating ipatasertib in combination with abiraterone and prednisone/prednisolone met one of its co-primary endpoints. News release. Roche. June 19, 2020. Accessed June 19, 2020. https://bit.ly/2YTndZh