CAPItello-290 Phase III Trial Update: Truqap + Chemo in Advanced/Metastatic Triple-Negative Breast Cancer

On June 18, 2024, the results of the CAPItello-290 Phase III trial were announced in London, UK. The trial evaluated the efficacy of Truquap (capivasertib) combined with paclitaxel in treating patients with locally advanced or metastatic triple-negative breast cancer (TNBC). Unfortunately, the trial did not meet its primary goals, which were to show improvement in overall survival (OS) when compared to paclitaxel combined with a placebo. This outcome was consistent both in the overall patient population and in a subgroup of patients whose tumors had specific biomarker alterations (PIK3CA, AKT1, or PTEN).

Breast cancer is the second most common cancer globally and is responsible for a significant number of cancer-related deaths. TNBC is a particularly aggressive form of the disease that lacks estrogen, progesterone receptors, and does not overexpress human epidermal growth factor receptor 2 (HER2). Standard treatment for advanced or metastatic TNBC typically includes chemotherapy, which has response rates between 30 to 50%. However, even in patients who initially respond to treatment, disease progression is often rapid, and the overall survival rate remains low, averaging 12 to 18 months. Only about 14% of patients survive five years post-diagnosis.

Dr. Peter Schmid from the Barts Cancer Institute in London, who was the principal investigator for the trial, noted the ongoing challenges in treating TNBC due to the lack of actionable biomarker targets. He emphasized the importance of the trial's findings for future research, even though the results were not as hoped. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, echoed this sentiment. She underscored AstraZeneca's commitment to advancing scientific understanding in challenging cancer subtypes, including TNBC.

The CAPItello-290 trial was a global, randomised, double-blind study that enrolled 923 adult patients with confirmed locally advanced or metastatic TNBC. The trial's primary endpoints were overall survival in both the general patient population and in those with tumors showing alterations in the PI3K/AKT pathway (PIK3CA, AKT1, or PTEN genes). Despite the disappointing outcome, the trial did not identify any new safety concerns for Truquap when used in combination with paclitaxel.

Truquap is a novel inhibitor targeting all three AKT isoforms (AKT1/2/3) and is taken twice daily. It has already been approved in the US, Japan, and other countries for treating HR-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations, following results from the CAPItello-291 trial.

AstraZeneca continues to conduct further Phase III trials involving Truquap for breast cancer (CAPItello-292) and prostate cancer (CAPItello-280 and CAPItello-281) in combination with established treatments. The company remains dedicated to understanding and addressing the complexities of various cancer types through persistent innovation and comprehensive research efforts.