Astra stumbles again with Truqap

AstraZeneca’s ambitions of making its AKT inhibitor Truqap a multi-blockbuster took a blow on Tuesday with failure of the pivotal CAPItello-280 trial in second-line castrate-resistant prostate cancer. The group is discontinuing the study following a pre-specified interim analysis, it disclosed in conjunction with its first-quarter earnings.

Detailed results aren’t yet available, but the failure comes not long after success in another prostate cancer setting, hormone-sensitive disease, in the CAPItello-281 study; however, that trial was limited to patients with PTEN-deficient tumours.

During a first-quarter media call AstraZeneca’s chief executive, Pascal Soriot, noted that different tumour types and subgroups vary, and that the company had always seen CAPItello-280 as the riskier prostate cancer phase 3.

Astra still believes Truqap “has good potential” in breast cancer; the drug is approved in second-line ER-positive, HER2-negative disease with PIK3CA/AKT1/PTEN alterations, while a first-line study, CAPItello-292, is set to readout after 2026. However, completion of CAPItello-292 has been pushed back more than once, and such delays are rarely a good sign.

Truqap has already failed in its first-line triple-negative breast cancer trial, CAPItello-290.

Prostate cancer fail

Castrate-resistant prostate cancer now also looks like a dead end after the failure of CAPItello-280, which tested Truqap plus docetaxel and androgen deprivation therapy (ADT), versus docetaxel and ADT, in patients previously treated with androgen receptor pathway inhibitors (ARPIs) like Zytiga or Xtandi.

The data monitoring committee concluded that the study was unlikely to meet its co-primary endpoints of radiographic progression-free survival and overall survival.

The trial didn’t require patients to have PTEN alterations, which be a factor behind the failure. The clinicaltrials.gov entry, meanwhile, mentions evaluating rPFS and OS by PTEN-deficient and proficient subgroups.

The castrate-resistant prostate cancer space is evolving, with radioligand therapies like Novartis’s Pluvicto now muscling into the post-ARPI population, and other groups like Janux also taking aim at second-line disease.

In light of the latest failure Soriot maintained that Truqap, which sold $430m in 2024, could eventually bring in $1-3bn, as predicted at Astra's May 2024 investor day. But he admitted that the latest miss means the drug’s sales potential will be smaller. The pressure is on in breast cancer.

Global phase 3 trials of Truqap

Note: ADT=androgen deprivation therapy. Source: OncologyPipeline & clinicaltrials.gov.