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AstraZeneca’s Truqap combo flops in Phase 3 triple-negative breast cancer trial

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AstraZeneca’s Truqap failed to boost survival in a late-stage test in certain patients with triple-negative breast cancer, dealing a blow to the company’s efforts to expand the drug’s label.

In the Phase 3 CAPItello-290 trial in triple-negative breast cancer (TNBC), the AKT inhibitor plus the chemotherapy paclitaxel did not meet the dual primary endpoints of overall survival improvement in either the overall population or the subgroup of patients with alterations in the PI3K/AKT pathway.

The placebo-controlled study was testing the regimen in 923 patients with first-line locally advanced or metastatic TNBC. The combination’s safety profile was consistent with the known safety of each medicine and no new concerns were identified, according to a company release.

Truqap was approved for the first time in November in combination with AstraZeneca’s Faslodex (fulvestrant) for advanced HR-positive HER-2 negative breast cancer, with its label limited to those patients with PIK3CA, AKT1 or PTEN genetic alterations. The drug achieved $50 million in sales in the first quarter of 2024.

The UK drugmaker has other chances to expand Truqap’s label. A combination of the AKT inhibitor plus Faslodex and a CDK4/6 inhibitor is being studied for certain forms of locally advanced, unresectable or metastatic breast cancer in the Phase 3 CAPItello-292 trial.

Truqap is also being evaluated as an add-on to established treatments in a pair of Phase 3 prostate cancer studies — CAPItello-280 and CAPItello-281.

CAPItello-281 will be the next to readout in the second half of the year, according to a company presentation. The trial is evaluating Truqap plus abiraterone and androgen deprivation therapy in participants with metastatic hormone-sensitive prostate cancer and PTEN deficiency.

In February last year, Roche’s own AKT inhibitor, ipatasertib, combined with abiraterone missed the key endpoint of overall survival in the Phase 3 IPATential150 study in certain first-line prostate cancer patients, despite hitting the trial’s progression-free survival co-primary endpoint. The drug is still being advanced at earlier phases for gastric and prostate cancers.

AstraZeneca said it will share results from the failed CAPItello-290 trial at a later date.


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