Clinical trial information
Select trial for more information
- Overview
- Clinical Trials
- Abbreviations
Target Overview
B7-H4 (VTCN1) is a cell-surface glycoprotein in the B7 protein family which contains the immune checkpoint receptors.1 B7-H4 is overexpressed in a range of solid tumors including endometrial cancer, ovarian cancer, breast cancer, biliary tract cancers and squamous NSCLC, and has very limited normal tissue expression, making it an attractive target for an antibody-drug conjugate.2,3
Compound Overview
Puxitatug samrotecan is comprised of an anti-B7-H4 human IgG1 monoclonal antibody attached to a topoisomerase I inhibitor (TOP1i) warhead (AZ’0132) via a cleavable linker. The primary mechanism of action of puxitatug samrotecan is intracellular delivery of the TOP1i warhead to B7-H4-expressing tumor cells, leading to DNA damage and apoptotic cell death. In addition, the cell permeable warhead can then diffuse out of B7-H4 positive cells to kill neighboring cells without B7-H4 expression, a mechanism called the bystander effect.4
Mechanism of Action
References
1. Smith JB, Stashwick C, Powell DJ. Gynecol Oncol. 2014;134(1):181-189. 2. Leong SR, Liang WC, Wu Y, et al. Mol Pharm. 2015;12(6):1717-1729. 3. Tringler B, Zhuo S, Pilkington G, et al. Clin Cancer Res. 2005;11(5):1842-1848. 4. Kinneer K, Wortmann P, Cooper ZA, et al. Clin Cancer Res. 2023;29(6):1086-1101.
Arrange By
Selected Filter(s)
Abbreviations
DNA
deoxyribonucleic acid
IgG1
immunoglobulin G1
Target Overview
B7-H4 (VTCN1) is a cell-surface glycoprotein in the B7 protein family which contains the immune checkpoint receptors.1 B7-H4 is overexpressed in a range of solid tumors including endometrial cancer, ovarian cancer, breast cancer, biliary tract cancers and squamous NSCLC, and has very limited normal tissue expression, making it an attractive target for an antibody-drug conjugate.2,3
Compound Overview
Puxitatug samrotecan is comprised of an anti-B7-H4 human IgG1 monoclonal antibody attached to a topoisomerase I inhibitor (TOP1i) warhead (AZ’0132) via a cleavable linker. The primary mechanism of action of puxitatug samrotecan is intracellular delivery of the TOP1i warhead to B7-H4-expressing tumor cells, leading to DNA damage and apoptotic cell death. In addition, the cell permeable warhead can then diffuse out of B7-H4 positive cells to kill neighboring cells without B7-H4 expression, a mechanism called the bystander effect.4
Mechanism of Action
References
1. Smith JB, Stashwick C, Powell DJ. Gynecol Oncol. 2014;134(1):181-189. 2. Leong SR, Liang WC, Wu Y, et al. Mol Pharm. 2015;12(6):1717-1729. 3. Tringler B, Zhuo S, Pilkington G, et al. Clin Cancer Res. 2005;11(5):1842-1848. 4. Kinneer K, Wortmann P, Cooper ZA, et al. Clin Cancer Res. 2023;29(6):1086-1101.
Clinical trial information
Select trial for more information
Arrange By
Selected Filter(s)
Abbreviations
DNA
deoxyribonucleic acid
IgG1
immunoglobulin G1