Ipatasertib meets one of two primary endpoints in Phase III trial


According to a media release issued by Roche earlier this morning, the company’s investigational drug known as ipatasertib met one but not both of the two primary endpoints in a randomized, double-blind Phase III trial known as the IPATential150 trial.

Ipatasertib was being tested in this trial for the treatment of men with asymptomatic or mildly symptomatic, metastatic, castration-resistant prostate cancer (mCRPC) who had not previously received treatment after progression to mCRPC. This means that they had to have received treatment with — and were still receiving — a standard form of androgen deprivation therapy (ADT) such as a bilateral orchiectomy or an LHRH agonist or antagonist, but they couldn’t have received treatment with anything like abiraterone acetate (Zytiga), enzalutamide (Xtandi), taxane chemotherapy, or radium-223 (Xofigo). All patients had to have a valid test for expression of the phosphatase and tensin homolog (PTEN) tumor suppressor protein. Loss of expression of this protein is believed to occur in 40 to 60 percent of men with mCRPC.

All patients were treated with either

  • Ipatasertib (400 mg once daily) and abiraterone (1,000 mg once daily without food) + prednisone (5 mg twice daily), administered orally, in 28-day cycles or
  • Placebo and abiraterone (1,000 mg once daily without food) + prednisone (5 mg twice daily), administered orally, in 28-day cycles

They also remained on whatever standard from of ADT they had already been receiving.

The primary study endpoint was radiogrphic progression-free survival (rPFS) as assessed by the investigator or death from any cause. However, this endpoint was assessed in two sets of patients:

  • The entire intent-to-treat set of 1,101 patients enrolled
  • The subset of patients known to have loss of PTEN expression

According to the media release issued by Roche earlier today, the primary endpoint in this study was met only for the subset of patients known to have loss of PTEN expression. It was not met for the entire intent-to-treat set of 1,101 patients enrolled in the trial. However, we do not have any detailed information about the trial’s results as yet. Roche has stated only that, “The results of the IPATential150 study will be presented at an upcoming medical meeting.”

It should also be noted that the trial is ongoing because one of the many secondary study endpoints is overall survival.

Based on this media release, it appears that — with respect to prostate cancer —  ipatasertib may receive regulatory approval for the treatment of men with asymptomatic or mildly symptomatic, previously untreated mCRPC who exhibit loss of function of the PTEN protein. Whether it may gain a broader indication for treatment of prostate cancer would seem to depend on other data still to come.

Ipatasertib is an investigational drug that targets and binds to the three subtypes (“isoforms”) of AKT (protein kinase B), which blocks the PI3K/AKT signalling pathway. This signaling pathway is a key driver of cancer cell growth and proliferation in prostate cancer. It has also been implicated in resistance to antiandrogen therapy as androgen receptor (AR) inhibition is associated with an increase in AKT pathway activation.

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