The US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) has recognised a favorable benefit risk profile for AstraZeneca’s TRUQAP (capivasertib) in combination with abiraterone and Androgen Deprivation Therapy (ADT) for the treatment of patients with PTEN-deficient metastatic Hormone-Sensitive Prostate Cancer (mHSPC), based on the CAPItello-281 phase 3 trial. The Committee voted 7 to 1, with 1 abstaining.

In August 2025, the FDA accepted the supplemental New Drug Application (sNDA) for TRUQAP in combination with abiraterone and ADT based on positive results from the CAPItello-281 phase 3 trial, presented at the 2025 European Society for Medical Oncology (ESMO) Congress and simultaneously published in Annals of Oncology.

Daniel George, MD, Director of Genitourinary Oncology, Duke Cancer Institute and investigator for the trial, said, “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.”

Results from the primary analysis of the CAPItello-281 phase 3 trial showed a statistically significant 19 percent reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic Progression-Free Survival (rPFS) of 7.5 months with the TRUQAP combination versus treatment with abiraterone and ADT with placebo (based on a Hazard Ratio [HR] of 0.81; 95 percent confidence interval [CI] 0.66-0.98; P=0.034). Median rPFS was 33.2 months for the TRUQAP combination versus 25.7 months for the comparator arm.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said, “CAPItello-281 is the first pivotal trial to prospectively define PTEN-deficient metastatic hormone-sensitive prostate cancer and its severe course of disease. The committee’s recognition of the unmet need in patients with PTEN-deficiency and of the benefit seen with the TRUQAP combination verifies its potential to address this significant need and optimise outcomes for patients. We are committed to working closely with the FDA to bring the first and only targeted treatment option to the one in four patients with this form of metastatic hormone-sensitive prostate cancer.”

A consistent benefit was observed with the TRUQAP combination versus treatment with abiraterone and ADT with placebo in key secondary endpoints of the trial, including prolonged time to castration resistance (29.5 vs. 22.0 months [HR 0.77; 95 percent CI: 0.63-0.94]) and Prostate-Specific Antigen (PSA) progression (HR 0.73; 95 percent CI: 0.52-1.01), and fewer and delayed events in terms of Symptomatic Skeletal Event-Free Survival (SSE-FS) (42.5 vs. 37.3 months [HR 0.82, 95 percent CI: 0.66-1.02]).

Overall Survival (OS) data were immature at the time of primary analysis; however, subsequent interim results for OS numerically favored the TRUQAP combination versus the comparator arm. The trial will continue as planned to further assess OS as a key secondary endpoint.

The safety profile of TRUQAP in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine. Consistent with the addition of a targeted treatment to background therapy, Grade 3 or higher adverse events occurred in 67 percent of patients treated with the TRUQAP combination versus 40.4 percent of patients treated with abiraterone and ADT with placebo. The most common Grade 3 or higher adverse events in the TRUQAP arm were rash (12.3 percent), hyperglycemia (10.3 percent), hypokalemia (8.7 percent), diarrhea (6.2 percent), hypertension (5.8 percent) and anemia (5.2 percent).

The ODAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA will consider the feedback as it reviews the submission and is not bound by the committee’s recommendation.

A regulatory application for TRUQAP in combination with abiraterone and ADT for the treatment of PTEN-deficient mHSPC is under review in the EU based on the CAPItello-281 phase 3 trial.