AstraZeneca's Truqap Fails in Phase III Triple-Negative Breast Cancer Trial

AstraZeneca recently announced that its AKT inhibitor Truqap (capivasertib), when paired with the chemotherapy drug paclitaxel, did not achieve its primary efficacy goal in the Phase III CAPItello-290 trial involving patients with metastatic triple-negative breast cancer (TNBC). The pharmaceutical company did not disclose detailed data, merely stating that the combination of Truqap and paclitaxel did not markedly improve overall survival rates either in the general study group or among patients with specific genetic mutations in the PIK3CA, AKT1, or PTEN genes. The clinical trial compared this treatment regimen against a placebo combined with paclitaxel.

AstraZeneca's executive vice president of oncology research and development, Susan Galbraith, expressed disappointment with the trial results. Despite the setback, Galbraith emphasized that these findings would enhance understanding of the PI3K/AKT pathway in breast cancer, contributing to the ongoing clinical research under the Truqap development program.

Triple-negative breast cancer is characterized by the absence of three commonly over-expressed receptors in breast cancer—estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2—which complicates its treatment. TNBC is also known for its aggressiveness and rapid progression. AstraZeneca reports that approximately 35% of TNBC cases involve alterations in the PIK3CA, AKT1, and PTEN proteins.

Truqap is a novel, ATP-competitive AKT inhibitor designed to block all AKT isoforms, thereby disrupting downstream signaling pathways that would otherwise promote uncontrolled cellular proliferation, invasion, and metastasis in TNBC. The drug received FDA approval in November 2023 for treating HR-positive, HER2-negative locally advanced or metastatic breast cancer in combination with AstraZeneca's endocrine therapy Faslodex (fulvestrant).

AstraZeneca aims to broaden the clinical application of Truqap by testing it in different types of breast cancer and various treatment settings. The CAPItello-290 trial is part of these efforts, alongside the Phase III CAPItello-292 study, which is evaluating Truqap in combination with Faslodex and palbociclib as a first-line treatment for patients with locally advanced, inoperable, or metastatic HR-positive, HER2-negative breast cancer.

Moreover, AstraZeneca is exploring the potential of Truqap in treating prostate cancer through the CAPItello-280 and CAPItello-281 trials.

This recent Phase III trial result marks a deviation from AstraZeneca's recent string of successes in oncology. For instance, the company's blockbuster drug Imfinzi (durvalumab) recently gained FDA approval for treating primary advanced or recurrent mismatch repair-deficient endometrial cancer. Additionally, AstraZeneca's BTK inhibitor Calquence (acalabrutinib) demonstrated significant survival benefits in the Phase III ECHO trial for mantle cell lymphoma when used in combination with bendamustine and rituximab.

Earlier this month, AstraZeneca also reported positive Phase III outcomes for Imfinzi in small cell lung cancer and the EGFR inhibitor Tagrisso (osimertinib) in EGFR-mutated non-small cell lung cancer.

These developments underscore AstraZeneca’s commitment to expanding its oncology portfolio despite the occasional clinical setback, aiming to offer novel therapies for challenging cancer types.