Antibody
RCSB PDB 9PI9
Payload
PubChem CID 104842
Sacituzumab govitecan
Trodelvy
- Mechanism of action
- Trop-2-targeted antibody-drug conjugate
- In plain language
- An antibody that homes in on Trop-2, a marker found on many tumor cells, delivering a potent chemotherapy drug directly into — and around — those cells to kill them, used against advanced triple-negative and HR-positive breast cancer.
- How it works
- Sacituzumab govitecan-hziy is an antibody-drug conjugate composed of the humanized antibody sacituzumab, which recognizes Trop-2, linked to the topoisomerase I inhibitor SN-38 via a hydrolyzable linker at a high average ratio of 7 to 8 drug molecules per antibody. The antibody binds Trop-2-expressing cancer cells and is internalized, after which lysosomal hydrolysis of the linker releases SN-38, which binds topoisomerase I and blocks re-ligation of the single-strand DNA breaks the enzyme normally repairs, driving apoptosis. Because the linker is only moderately stable, published pharmacology studies have also documented a 'bystander effect' in which some released SN-38 escapes into the surrounding tumor microenvironment and reaches neighboring cells regardless of their own Trop-2 status — a detail not spelled out in the FDA label's own mechanism section, but consistent with the drug's broad activity across HR-positive and triple-negative breast cancer.
- Therapeutic applications
- FDA-approved for three breast cancer indications: as a single agent for first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) in patients who are not candidates for PD-1/PD-L1 inhibitor-based therapy; in combination with pembrolizumab for first-line treatment of unresectable locally advanced or metastatic TNBC whose tumors express PD-L1; for second-line-or-later treatment of unresectable locally advanced or metastatic TNBC after two or more prior systemic therapies; and for unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer after endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
- Class
- Antibody-drug conjugate
- Therapeutic area
- Oncology
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