{"entity":{"id":"puxitatug-samrotecan","kind":"drug","name":"Puxitatug samrotecan","aka":[],"tldr":"Puxitatug samrotecan is a B7-H4 ADC targeting a checkpoint-like protein enriched in breast, ovarian, and endometrial cancers.","summary":"Puxitatug samrotecan is AstraZeneca's anti-B7-H4 IgG1 antibody carrying the topoisomerase I inhibitor AZ14170133 at a drug-to-antibody ratio of about 8 through a cleavable linker; the released payload traps topoisomerase I on DNA and crosses membranes to kill neighbouring cells. B7-H4 is a checkpoint-like protein enriched in breast, ovarian and endometrial cancers with minimal normal expression, and it is inversely correlated with PD-L1, offering a route into 'cold' tumours that immunotherapy fails to reach. The drug is in phase 2 dose optimisation on an every-3-weeks schedule in endometrial, ovarian and triple-negative breast cancer. Nausea, neutropenia and fatigue are the reported toxicities. Whether B7-H4 expression predicts response remains open. It targets a protein common in gynaecological and breast cancers that immunotherapy tends to miss.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Puxitatug samrotecan","url":"https://clinicaltrials.gov/search?intr=AZD8205"}],"tags":[],"related":[],"cancers":["tnbc","ovarian","endometrial"],"sections":[],"technologies":["adc"],"targets":["b7h4"],"drugs":[],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07044336","nct05123482"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"AZD8205","modality":"ADC","payload":"TOP1 inhibitor (AZ14170133), DAR ~8","linker":"Cleavable","mechanism":"Anti-B7-H4 IgG1 with TOP1 inhibitor.","approvals":[],"mechanismSteps":["Antibody binds B7-H4 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","TOP1 inhibitor is released inside the cell","Topoisomerase-I is trapped on DNA; replication forks collapse into double-strand breaks","Tumour cell dies by apoptosis","Membrane-permeable payload diffuses to kill neighbouring antigen-negative cells (bystander effect)"],"dosing":{"route":"IV infusion","schedule":"Phase 2 dose-optimisation; every 3 weeks","source":"https://clinicaltrials.gov/study/NCT05123482"},"toxicity":[{"event":"Nausea"},{"event":"Neutropenia"},{"event":"Fatigue"}],"access":[{"country":"US","reimbursement":"Investigational","asOf":"2026-09-06"}],"regulatoryEvents":[]},"route":"/drugs/puxitatug-samrotecan/","neighbours":{"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"b7h4","kind":"target","name":"B7-H4 (VTCN1)","route":"/targets/b7h4/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"trial":[{"id":"nct05123482","kind":"trial","name":"A Phase I/IIa Study of AZD8205 Given Alone or Combined, in Participants With Advanced/Metastatic Solid Malignancies","route":"/trials/nct05123482/"},{"id":"nct07044336","kind":"trial","name":"Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01)","route":"/trials/nct07044336/"}],"term":[{"id":"exatecan","kind":"term","name":"Exatecan (and derivatives)","route":"/terms/exatecan/"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","route":"/terms/topoisomerase-i-payloads/"}]}}