AstraZeneca’s Truqap Flops in Phase III Triple-Negative Breast Cancer Trial
18 Jun 2024
Phase 3Drug ApprovalClinical Result
Pictured: AstraZeneca's manufacturing facility in Sweden/iStock, Fotonen
AstraZeneca on Tuesday announced that its AKT inhibitor Truqap (capivasertib), when used in combination with paclitaxel, failed to meet its primary efficacy endpoint in the Phase III CAPItello-290 study in patients with metastatic triple-negative breast cancer.
The pharma did not provide specific data in its announcement, only revealing that the Truqap combo failed to significantly improve overall survival in the total study population or in the subgroup of patients with specific mutations in the PIK3CA, AKT1 or PTEN genes. The study compared the Truqap regimen against placebo plus paclitaxel.
Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, in a statement said that the pharma is “disappointed” by Tuesday’s readout. Nevertheless, Galbraith said “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.”
In patients with triple-negative breast cancer (TNBC), tumor cells lack the three most commonly over-expressed receptors in breast cancers—estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2—making them more difficult to target and treat. TNBCs are also typically more aggressive and tend to progress more rapidly.
Approximately 35% of TNBC cases show alterations in the PIK3CA, AKT1 and PTEN proteins, according to AstraZeneca. Truqap, a first-in-class and ATP-competitive blocker of AKT, is designed to address an underlying disease pathway in TNBC by blocking all AKT isoforms and disrupting their downstream cascades that would otherwise result in uncontrolled cell proliferation, invasion and metastasis.
The FDA approved Truqap in November 2023 for the treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer, when used in combination with AstraZeneca’s endocrine therapy Faslodex (fulvestrant).
The pharma has been trying to expand Truqap’s patient pool by testing it in other types of breast cancer and in other settings of care. CAPItello-290 is part of this push, alongside the Phase III CAPItello-292 study, which is testing the AKT inhibitor with Faslodex and palbociclib as a first-line triplet regimen in patients with locally advanced, inoperable or metastatic HR-positive or HER2-negative breast cancer.
AstraZeneca is also assessing Truqap in prostate cancer, for which it is running the CAPItello-280 and CAPItello-281 trials.
Tuesday’s Phase III flop breaks AstraZeneca’s recent winning streak in cancer. On Monday, the pharma’s blockbuster drug Imfinzi (durvalumab) won the FDA’s approval for primary advanced or recurrent mismatch repair-deficient endometrial cancer. A day before, AstraZeneca reported that its BTK inhibitor Calquence (acalabrutinib) aced the Phase III ECHO trial, demonstrating significant and meaningful survival benefits when used with bendamustine and rituximab to treat mantle cell lymphoma.
Earlier this month, AstraZeneca also recorded Phase III wins for Imfinzi in small cell lung cancer and for the EGFR inhibitorEGFR inhibitor Tagrisso (osimertinib) in EGFR-mutated non-small cell lung cancer.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
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