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trastuzumab deruxtecan + capivasertib
- Development stage
- Phase 1
- Lead developer
- AstraZeneca
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Trastuzumab deruxtecan (T-DXd) + capivasertib is an investigational combination therapy for the treatment of advanced or metastatic breast cancer. Trastuzumab deruxtecan is an antibody-drug conjugate (ADC) consisting of an anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload via a cleavable tetrapeptide-based linker. Capivasertib is an orally bioavailable, selective pan-AKT inhibitor targeting AKT1/2/3. The combination leverages T-DXd’s targeting of HER2-expressing tumor cells and direct cytotoxicity, alongside capivasertib’s inhibition of the PI3K/AKT signaling pathway downstream of HER2. This approach aims to enhance tumor cell death and inhibit resistance mechanisms, especially in tumors harboring PI3K pathway mutations. Preclinical and early clinical evidence indicates preliminary antitumor activity in HER2-low and HER2+ metastatic breast cancer, including cases with PIK3CA or PTEN mutations.
- Brand names
- Enhertu + capivasertib
- Other names
- T-DXd + capivasertib
02
Targets
AKT1 (Proto-oncogene serine/threonine-protein kinase Akt1)AKT2 (Rac-beta serine/threonine-protein kinase)AKT3 (RAC-gamma serine/threonine-protein kinase)ERBB2 (Erb-b2 receptor tyrosine kinase 2)
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