# Puxitatug samrotecan

Source: https://onco.cc/drugs/puxitatug-samrotecan/  
OnCo record `puxitatug-samrotecan` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: phase-2
- Last checked: 2026-09-04
- Code: AZD8205
- Modality: ADC
- Mechanism: Anti-B7-H4 IgG1 with TOP1 inhibitor.
- Payload: TOP1 inhibitor (AZ14170133), DAR ~8
- Linker: Cleavable
- Dosing: IV infusion; Phase 2 dose-optimisation; every 3 weeks

## Sources

- ClinicalTrials.gov: trials of Puxitatug samrotecan: https://clinicaltrials.gov/search?intr=AZD8205

## Connected records

- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [B7-H4 (VTCN1)](https://onco.cc/targets/b7h4/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- trials: [A Phase I/IIa Study of AZD8205 Given Alone or Combined, in Participants With Advanced/Metastatic Solid Malignancies](https://onco.cc/trials/nct05123482/), [Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01)](https://onco.cc/trials/nct07044336/)
- terms: [Exatecan (and derivatives)](https://onco.cc/terms/exatecan/), [Topoisomerase-I inhibitor payloads](https://onco.cc/terms/topoisomerase-i-payloads/)

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JSON: https://onco.cc/api/v1/entities/puxitatug-samrotecan.json