FDA Advisory Committee Backs Truqap Combination for PTEN-Deficient Metastatic HS Prostate Cancer

AstraZeneca announced that the FDA’s Oncologic Drugs Advisory Committee voted 7 to 1, with 1 abstention, that Truqap plus abiraterone and androgen deprivation therapy has a favorable benefit-risk profile for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer. The recommendation is based on CAPItello-281, a Phase III trial showing a statistically significant improvement in radiographic progression-free survival.

Truqap, also known as capivasertib, is currently under FDA review through AstraZeneca’s supplemental New Drug Application. While the FDA is not required to follow ODAC recommendations, the committee’s vote provides important expert input as the agency evaluates the proposed indication.

“Patients identified to have PTEN-deficient metastatic hormone-sensitive prostate cancer have an aggressive form of the disease and currently experience poor outcomes. Their disease significantly impacts their quality of life and inevitably progresses to more advanced stages that are associated with high mortality rates. In addition to this poor prognosis, patients currently have limited treatment options, which is why today’s recommendation of the capivasertib combination is welcome news for both patients and clinicians to address an urgent need for new treatments that delay progression,” said Dr. Daniel George, Director of Genitourinary Oncology at Duke Cancer Institute and investigator for the trial.

CAPItello-281 met its primary endpoint

CAPItello-281 was a global, Phase III, double-blind, randomized trial enrolling 1,012 adults with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency confirmed by central testing. Patients received Truqap plus abiraterone and ADT or abiraterone and ADT with placebo.

At the primary analysis, the Truqap combination reduced the risk of radiographic disease progression or death by 19% compared with abiraterone and ADT plus placebo. Median radiographic progression-free survival was 33.2 months with the Truqap regimen versus 25.7 months in the comparator arm, representing a 7.5-month improvement. The hazard ratio was 0.81, with a 95% confidence interval of 0.66 to 0.98 and a p value of 0.034.

Benefit was also observed across key secondary endpoints. Time to castration resistance was prolonged with the Truqap combination, 29.5 months versus 22.0 months, with a hazard ratio of 0.77. PSA progression also favored the Truqap arm, with a hazard ratio of 0.73. Symptomatic skeletal event-free survival was 42.5 months with the Truqap regimen versus 37.3 months in the comparator arm, with a hazard ratio of 0.82.

Overall survival data were immature at the primary analysis. AstraZeneca reported that subsequent interim OS results numerically favored the Truqap combination, and the trial will continue to assess OS as a key secondary endpoint.

Safety profile reflects added targeted therapy

The safety profile of Truqap in combination with abiraterone and ADT was broadly consistent with the known profiles of the individual medicines. However, Grade 3 or higher adverse events were more frequent in the Truqap arm, occurring in 67% of patients, compared with 40.4% in the abiraterone, ADT, and placebo arm.

The most common Grade 3 or higher adverse events in patients receiving Truqap were rash, reported in 12.3%, hyperglycemia in 10.3%, hypokalemia in 8.7%, diarrhea in 6.2%, hypertension in 5.8%, and anemia in 5.2%.

Truqap is a first-in-class, ATP-competitive inhibitor of all three AKT isoforms: AKT1, AKT2, and AKT3. It is administered at 400 mg twice daily on an intermittent schedule of four days on and three days off, a regimen selected in early-phase studies to balance tolerability with target inhibition.

The FDA accepted the application in August 2025 after positive CAPItello-281 data were presented at the 2025 European Society for Medical Oncology Congress and published simultaneously in Annals of Oncology. A regulatory application for the same indication is also under review in the European Union.

If approved, the combination would become the first targeted treatment option for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer, a subgroup with substantial unmet need and limited treatment choices.