AstraZeneca’s Truqap Fails to Meet Primary Endpoints in Phase III Trial for Locally Advanced or Metastatic Triple-Negative Breast Cancer

Image Credit: Adobe Stock Images/Sebastian Kaulitzki

Results from the Phase III CAPItello-290 trial evaluating AstraZeneca’s Truqap (capivasertib) in combination with paclitaxel for patients with locally advanced or metastatic triple-negative breast cancer (TNBC) did not meet its primary goals. According to the company, the study failed to improve overall survival (OS) compared to paclitaxel with a placebo, both in the overall patient population and in a subgroup with specific biomarker alterations (PIK3CA, AKT1, or PTEN).¹

“Despite modest advances, [TNBC] remains one of the most challenging forms of disease to treat due to the lack of known actionable biomarker targets, and chemotherapy-based regimens continue to be the mainstay of treatment,” said Peter Schmid, MD, Barts Cancer Institute, London, UK, principal investigator of the trial, in a press release. “While the CAPItello-290 trial results have not shown what we hoped, they provide important information to further understand this aggressive form of breast cancer where patients are in urgent need of new treatments.”

Truqap is a first-in-class, potent, adenosine triphosphate-competitive inhibitor of the three AKT isoforms (AKT1/2/3). The therapy is administered at a dose of 400 mg twice daily following an intermittent dosing schedule of four days on and three days off. Truqap has been previously approved by the FDA to treat adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) after recurrence or progression on or following an endocrine-based treatment regimen.

The double-blind, randomized CAPItello-290 trial evaluated the efficacy and safety of Truqap in combination with paclitaxel versus placebo in combination with paclitaxel in the first-line treatment of patients with locally advanced (inoperable) or metastatic TNBC. The trial enrolled 923 adults with a history of locally advanced or metastatic TNBC. The dual primary endpoints of the trial were OS in the overall patient population and in patients with tumors that have qualifying alterations in the PI3K/AKT pathway. The safety profile of the combination of Truqap and chemotherapy was consistent with known data, showing no new safety concerns. AstraZeneca intends to share the full data from the study at a later date.

AstraZeneca states that TNBC is one of the most difficult-to-treat cancers due to the limited number of targeted biomarker treatments, with chemotherapy remaining the primary treatment. Reportedly, IK3CA, AKT1, and PTEN mutations affect around 35% of TNBC patients. Overall, breast cancer is the second most common cancer worldwide and one of primary drivers of cancer death.¹

According to WebMD, approximately 60% of patients with TNBC will survive over five years without disease, but for an estimated four in 10 women will experience rapid recurrence. TNBC grows quicker than other breast cancers, with one study finding that it grows by 1% each day from diagnosis to surgery, compared to 0.859% for HER2-positive breast cancer. By the time it has been found, it is likely that TNBC has spread beyond the breast, and it has a higher probability of being more fatal within the first five years of treatment.²

“We are committed to advancing science for patients in some of the most challenging cancers, including this heterogeneous subtype of breast cancer. 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 program and across our pipeline,” said Susan Galbraith, EVP, Oncology R&D, AstraZeneca, in the press release.

References

1. Update on the CAPItello-290 Phase III trial for Truqap plus chemotherapy in advanced or metastatic triple-negative breast cancer. AstraZeneca. June 18, 2024. Accessed June 19, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/update-on-capitello-290-phase-iii-trial.html 

2. Triple-Negative Breast Cancer (TNBC). WedMD. February 20, 2024. Accessed June 19, 2024. https://www.webmd.com/breast-cancer/triple-negative-breast-cancer