- Clinical Pipeline
- Guadecitabine (SGI-110) DNMT inhibitor (Hematological Malignancies and Solid Tumors)
- ASTX029 Extracellular Signal-Related Protein Kinases (ERK 1/2) Inhibitor (Solid Tumors)
- Oral Decitabine and Cedazuridine (ASTX727) (Hematological Malignancies)
- ASTX660 Dual IAP Antagonist (Solid Tumors & Lymphomas)
- ASTX295 Oral Murine Double Minute 2 (MDM2) antagonist (Solid Tumors)
- Partnered Products and Programs
- Kisqali®(ribociclib) CDK4/6 inhibitor (Oncology)
- Balversa® (erdafitinib) FGFr inhibitor (Oncology)
- AZD5363 PKB/Akt Inhibitor (Oncology)
- Multiple Targets and Therapeutic Areas
- Pyramid™ Discovery Platform
- Oncology and CNS Discovery
- Sustaining Innovation
|Discovery||Phase 1||Phase 2||Phase 3||Marketed|
PKB/Akt Inhibitor (Oncology)
Mechanism of Action: Protein kinase B (PKB) / serine/threonine protein kinase (AKT) inhibition
Discovery: Derived from a collaborative drug discovery program between AstraZeneca, Astex Pharmaceuticals, The Institute of Cancer Research (ICR) and Cancer Research Technology Limited (CRT). The program began in 2003 through Astex Pharmaceuticals’ collaboration with ICR and CRT. The collaboration with AstraZeneca commenced in July 2005.
How this therapy can help
AZD5363 binds to and inhibits all AKT isoforms. Inhibition of AKT prevents the phosphorylation of AKT substrates that mediate cellular processes, such as cell division, apoptosis, and glucose and fatty acid metabolism. A wide range of solid and hematological malignancies show dysregulated PI3K/AKT/mTOR signalling due to mutations in multiple signalling components. By targeting AKT, the key node in the PIK3/AKT signalling network, this agent may be used as monotherapy or combination therapy for a variety of human cancers.
Inhibition of the PKB/AKT pathway has potential in the treatment of a broad range of tumor types.
Capivasertib (AZD5363) has completed the CAPItello-291 Phase 3 trial in combination with Faslodex (fulvestrant) versus Faslodex alone in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low or negative locally advanced or metastatic breast cancer. CAPitello-291 met both primary endpoints demonstrating improvement in progression-free survival (PFS) in the overall patient population and in a prespecified biomarker subgroup of patients whose tumours had qualifying alterations in the PIK3CA, AKT1 or PTEN genes. AstraZeneca is seeking Marketing Approval from the US FDA. AstraZeneca is also investigating capivasertib in several other breast cancer as well as prostate cancer clinical studies.
For breast cancer, this includes a Phase 3 study of capivasertib plus paclitaxel as a first-line treatment for patients with histologically confirmed, locally advanced (inoperable) or metastatic triple negative breast cancer, while a phase 1b/3 study of capivasertib plus palbociclib and fulvestrant is being examined in hormone receptor-positive and human epidermal growth factor receptor 2-negative locally advanced, unresectable or metastatic breast cancer.
For prostate cancer, capivasertib is being investigated in a phase 3 clinical trial as a monotherapy. There are also several ongoing capivasertib combination phase 3 studies including capivasertib plus docetaxel as treatment for patients with metastatic castration resistant prostate cancer (mcrpc), and capivasertiib plus abiraterone as a treatment for patients with de novo metastatic hormone-sensitive prostate cancer characterised by PTEN deficiency.