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trastuzumab deruxtecan + olaparib
- Development stage
- Phase 1
- Lead developer
- Daiichi Sankyo
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Trastuzumab deruxtecan + olaparib is a combination therapy being investigated for the treatment of HER2-expressing solid tumors, including platinum-resistant high-grade serous ovarian carcinoma. Trastuzumab deruxtecan (Enhertu) is a HER2-directed antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload (deruxtecan) via a tetrapeptide-based cleavable linker. Olaparib (Lynparza) is a small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. The rationale for this combination is to exploit the DNA-damaging effects of the topoisomerase I inhibitor payload delivered by the ADC and the DNA repair inhibition provided by the PARP inhibitor, potentially leading to synergistic antitumor activity in tumors with HER2 expression and DNA repair vulnerabilities.
- Other names
- T-DXdtrastuzumab deruxtecanolaparib
02
Targets
ERBB2 (Erb-b2 receptor tyrosine kinase 2)PARP1 (Poly (adp-ribose) polymerase 1)PARP2 (Poly (adp-ribose) polymerase 2)
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