AstraZeneca has been dealt a blow after its flagship breast cancer drug Truqap (capivasertib) did not improve overall survival (OS) in a Phase III TNBC trial.
The Truqap and chemotherapy (paclitaxel) combo in the Phase III CAPItello-290 trial failed to meet its dual primary endpoints of improvement in OS versus chemotherapy and placebo in either the overall trial population or in a subgroup of patients that had tumours with specific biomarker alterations (PIK3CA, AKT1 or PTEN).
According to research, mutations in PIK3CA, AKT1 and alterations in PTEN affect approximately 35% of patients with TNBC.
The Phase III, double-blind, randomised trial (NCT03997123) evaluated the efficacy of Truqap in combination with chemotherapy in patients with locally advanced (inoperable) or metastatic TNBC.
The safety profile of Truqap in combination with paclitaxel in CAPItello-290 was broadly consistent with the known safety profile of each medicine.
AstraZeneca’s executive vice-president for oncology R&D, Susan Galbraith, said: “While we are disappointed in the CAPItello-290 outcome, these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the Truqap clinical development programme and across our pipeline.”
Truqap is a first-in-class adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3).
AstraZeneca has other ongoing Phase III trials for the drug, one in breast cancer, CAPItello-292, (NCT04862663) and two in prostate cancer in CAPItello-280 (NCT05348577) and CAPItello-281 (NCT04493853).
This recent blow comes after Truqap received approval from the US Food and Drug Administration (FDA) in 2023, in combination with Faslodex (fulvestrant) for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer with one or more AKT pathway mutations.
While AstraZeneca originally hoped for approval for all HR+/HER- patients, the FDA only approved Truqap for patients with AKT pathway mutations despite statistical significance in its primary endpoint in the wider patient population.
The same combination was also recommended for approval in Europe in April 2024.
This more limited approval from the US body was due to the smaller effect on PFS in the wider population and the unfavourable safety profile, with 13% of patients discontinuing treatment in the experimental arm of the trial compared with just 2.3% in the placebo arm, as per GlobalData analysts.
GlobalData is the parent company of Clinical Trials Arena.
Elsewhere in TNBC trials, Merck & Co (MSD) recently reported that its Phase III KEYNOTE-522 trial (NCT03036488) of its flagship drug Keytruda to treat high-risk, early-stage TNBC met its OS endpoint.
