AstraZeneca's Truqap (capivasertib) received a positive recommendation from the US FDA's Oncologic Drugs Advisory Committee (ODAC) for use in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC), a vote that follows the agency's acceptance of a supplemental New Drug Application (sNDA) in August 2025. The committee voted 7 to 1, with one abstention, in favor of the benefit-risk profile of capivasertib in combination with abiraterone and androgen deprivation therapy (ADT). The ODAC recommendation does not constitute a final FDA approval decision, and the agency is not bound by the committee's conclusions.
The sNDA seeks approval for Truqap in combination with abiraterone and ADT for adult patients with PTEN-deficient mHSPC, a subgroup estimated to represent approximately one in four patients diagnosed with the disease in the US each year. Truqap is administered at 400 mg twice daily on an intermittent schedule of four days on and three days off. AstraZeneca has also submitted a regulatory application for the same indication in the European Union, where it remains under review. The company has not disclosed a specific PDUFA date in connection with the US filing.
The submission is supported by results from the CAPItello-281 Phase III trial, a double-blind, randomized, placebo-controlled study that enrolled 1,012 adults with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and centrally confirmed PTEN deficiency. Patients were randomized to receive either capivasertib plus abiraterone and ADT or placebo plus abiraterone and ADT. The primary endpoint was radiographic progression-free survival (rPFS) as assessed by the investigator.
Results from the primary analysis, presented at the 2025 European Society for Medical Oncology Congress and simultaneously published in the Annals of Oncology, showed a statistically significant 19% reduction in the risk of radiographic disease progression or death with the capivasertib combination, corresponding to a hazard ratio of 0.81 (95% CI: 0.66–0.98; p=0.034). Median rPFS was 33.2 months in the capivasertib arm versus 25.7 months in the comparator arm, a difference of 7.5 months. Secondary endpoints showed consistent directional benefit: time to castration resistance was 29.5 versus 22.0 months (HR 0.77; 95% CI: 0.63–0.94), and symptomatic skeletal event-free survival was 42.5 versus 37.3 months (HR 0.82; 95% CI: 0.66–1.02). PSA progression favored the capivasertib arm with an HR of 0.73 (95% CI: 0.52–1.01). Overall survival data were immature at the time of the primary analysis, though interim results numerically favored the capivasertib combination; the trial is ongoing to assess OS as a key secondary endpoint.
The safety profile observed in CAPItello-281 was broadly consistent with the known profiles of each component. Grade 3 or higher adverse events occurred in 67% of patients in the capivasertib arm versus 40.4% in the placebo arm. The most common high-grade events in the capivasertib group included rash (12.3%), hyperglycemia (10.3%), hypokalemia (8.7%), diarrhea (6.2%), hypertension (5.8%), and anemia (5.2%).