Truqap could fill a prostate cancer gap
The AKT inhibitor prevails in hormone-sensitive disease, but other studies have been delayed.
The AKT inhibitor prevails in hormone-sensitive disease, but other studies have been delayed.
AstraZeneca’s AKT inhibitor Truqap has had its ups and downs, but it could soon add a prostate cancer niche to its approved breast cancer use: the company said on Monday that the drug had succeeded in the CAPItello-281 study in first-line hormone-sensitive prostate cancer (HSPC).
The trial was limited to patients with PTEN-deficient disease; in breast cancer, Truqap is only approved for those with PIK3CA/AKT1/PTEN alterations, despite having shown a benefit in all comers. The drug is in several more late-stage trials, in both breast and prostate cancer, but readouts have been delayed which is rarely a good sign.
Phase 3 trials of Truqap
| Setting | Study | Primary endpoint | Outcome |
|---|---|---|---|
| HR+/HER2- breast cancer | CAPItello-291 (2nd-line, +Faslodex) | PFS | +ve for PFS in all-comers & in PIK3CA/AKT1/PTEN-altered subgroup; US approved for PIK3CA/AKT1/PTEN-altered in Nov 2023 |
| CAPItello-292 (1st-line, +CDK4/6 inhibition +Faslodex) | PFS | Ends Nov 2027 (delayed from Oct 2025, then Aug 2026) | |
| 1st-line TNBC | CAPItello-290 | OS | Failed for OS in all-comers and in PIK3CA/AKT1/PTEN-altered subgroup in Jun 2024 |
| 1st-line hormone-sensitive prostate cancer | CAPItello-281 (PTEN-altered, Zytiga combo) | rPFS | Toplined positive Nov 2024 |
| Castration-resistant prostate cancer | CAPItello-280 (2nd-line) | OS | Ends Dec 2026 (delayed from Jul 2026, then Oct 2026) |
Source: OncologyPipeline & clinicaltrials.gov.
CAPItello-281 tests Truqap plus Zytiga plus androgen deprivation therapy, versus Zytiga and androgen deprivation therapy alone. All Astra is saying for now is that it met its primary endpoint, radiographic progression-free survival, and that there was an “early trend” towards an overall survival benefit, although OS data are immature.
Astra estimates that, of the 200,000 patients diagnosed with metastatic HSPC every year, around a quarter have PTEN-deficient tumours.
Various other groups are developing AKT inhibitors, but none for HSPC, according to OncologyPipeline.
Astra is also making efforts in castration-resistant prostate cancer, but here the CAPItello-280 trial has been delayed a couple of times, and is now expected to complete in late 2026. This study also doesn’t appear to select for PTEN-deficiency.
Rivals in CRPC include China’s Laekna, which got the FDA go ahead in May to start a phase 3 trial of its AKT inhibitor afuresertib plus its CYP17A1/CYP11B2 dual inhibitor LAE001 in second-line disease.
Breast cancer
In breast cancer, Truqap is marketed in second-line HR-positive HER2-negative breast cancer, but Astra’s efforts to expand into first-line triple-negative fell flat this year with the comprehensive failure of the CAPItello-290 trial.
Again, Astra has other irons in the fire: CAPItello-292 tests Truqap plus Faslodex plus CDK4/6 inhibitors in first-line HR-positive HER2-negative disease. Again, this trial has been delayed, and doesn’t require patients to have PIK3CA/AKT1/PTEN alterations, although patients will be stratified based on testing.
Laekna also has trials ongoing with afuresertib in both HR-positive HER2-negative and triple-negative breast cancer.
However, in general AKT inhibition hasn’t lived up to expectations. Roche discontinued development of its contender ipatasertib, and Merck has gone quiet on miransertib, a project gained via its 2019 acquisition of Arqule.
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