U.S. Food and Drug Administration ODAC backs AstraZeneca’s Truqap combination for PTEN-deficient mHSPC, showing improved progression-free survival in the Phase III CAPItello-281 trial.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) has voted 7–1, with one abstention, in favour of a positive benefit–risk profile for AstraZeneca’s Truqap in combination with abiraterone and androgen deprivation therapy (ADT) for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC).
Truqap is an oral AKT inhibitor targeting AKT1/2/3 and is designed to block the PI3K/AKT pathway implicated in tumour growth. It is already approved in multiple regions, including the US and EU, in combination with fulvestrant for biomarker-selected advanced breast cancer, and is being evaluated in Phase III trials in breast and prostate cancer.
The recommendation follows acceptance of a supplemental New Drug Application in August 2025 based on results from the Phase III CAPItello-281 trial (NCT04493853), presented at the European Society for Medical Oncology Congress and published in Annals of Oncology.
In the CAPItello-281 trial, the Truqap combination showed a statistically significant 19% reduction in the risk of radiographic disease progression or death compared with abiraterone and ADT alone (hazard ratio 0.81; p=0.034), with a 7.5-month improvement in median radiographic progression-free survival (33.2 vs. 25.7 months).
Secondary endpoints were consistent with this benefit, including delayed time to castration resistance (29.5 vs. 22.0 months; HR 0.77), delayed prostate-specific antigen progression (HR 0.73), and fewer symptomatic skeletal events (42.5 vs. 37.3 months; HR 0.82).
Overall survival data remain immature, although interim results numerically favoured the combination, and the study is ongoing. The safety profile was consistent with known effects of the individual therapies, with Grade 3 or higher adverse events reported in 67% of patients receiving the Truqap combination compared with 40.4% in the control arm. The most common severe adverse events included rash, hyperglycaemia, hypokalaemia, diarrhoea, hypertension, and anaemia.
Investigators noted that PTEN-deficient mHSPC represents an aggressive disease subtype with limited treatment options and poor outcomes, and that the combination may help delay disease progression.
AstraZeneca stated that the trial is the first to prospectively define this subgroup and demonstrate benefit with an AKT inhibitor-based regimen, and that it plans to work with regulators to advance a targeted treatment option for this population, which accounts for approximately one in four patients with mHSPC.
The FDA will consider ODAC’s recommendation but is not bound by it. A final decision is pending, while a corresponding application is under review in the European Union.
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About the Writer
Samiksha Vikram Jadhav is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.