After a recent failed showing in a breast cancer subgroup raised doubts around AstraZeneca’s Truqap, the first-in-class AKT inhibitor is making inroads in a prostate cancer subtype.

High-level results from the company’s ongoing CAPltello-281 phase 3 study demonstrated that a combination of Truqap, Johnson & Johnson's Zytiga and androgen deprivation therapy (ADT) delivered statistically significant and clinically meaningful improvements on the trial’s primary endpoint of radiographic progression-free survival (rPFS), AZ said on Monday.

The trial compared the regimen versus the standard-of-care Zytiga and ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC), a specific type of prostate cancer with a particularly poor prognosis, AZ said in its Monday press release.

“By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need,” AZ's executive vice president of oncology R&D, Susan Galbraith, explained in the release. The results prove “for the first time” that adding an AKT inhibitor to standard-of-care therapy can provide a benefit in the patient group, Galbraith added.

While data for the key secondary endpoint of overall survival weren't mature at the time of analysis, the combo achieved an early trend toward extending lives in the 1,012-patient trial, the company said.

The results come after a prior stumble for the AKT inhibitor class in prostate cancer as Roche last year scrapped development of ipatasertib. That candidate showed a tumor progression benefit in a study of patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN loss, but it couldn’t show a significant impact on overall survival. AZ is also targeting the mCRPC patient group in a separate Truqap trial.

Meanwhile, for AZ, Truqap’s win is likely a welcome relief after a recent trial miss. The drug’s initial FDA approval last November was a limited one, covering only specific gene-altered patients with HR-positive, HER2-negative advanced breast cancer. Then, in September, AZ revealed a miss in a trial of patients with newly diagnosed metastatic triple-negative breast cancer and in a subgroup of patients with gene alterations.

In that study, the death risks between chemo and a combination of Truqap and chemotherapy paclitaxel were roughly the same at a median of 17.7 months for the treatment side and 18 months for the control group. In patients with the gene-altered tumors, the median survival rate was the same at 20.4 months between the two groups. Plus, some adverse events were observed at higher rates for Truqap-treated patients and led to more discontinuations in that arm. 

The company is still following that study to obtain a longer overall survival analysis and is also evaluating the drug in other breast cancer and prostate cancer patient populations.