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B7-H4 TOP1i ADC

CompoundPuxitatug samrotecan (AZD8205)

Area under investigation

Advanced solid tumors, HR-positive/HER2-negative breast cancer, BTCs, Endometrial cancer, Ovarian cancer

Scientific PillarAntibody-Drug Conjugates

 

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Bluestar-Endometrial01 trial overview

Tumor
B7-H4-selected advanced/metastatic endometrial cancer

Trial Identifier
NCT07044336

Phase
III

Regimen
Puxitatug samrotecan; doxorubicin/paclitaxel

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Study Design

Bluestar-Endometrial01

Inclusion criteria

The key inclusion criteria are –

  • Histologically confirmed diagnosis of EC or carcinosarcoma
  • Recurrent/metastatic EC (with radiological or objective evidence of recurrence or progression)
  • Received prior platinum-based chemotherapy and anti-PD-1/anti- PD-L1 therapy, either separately or in combination
  • ECOG PS of 0 or 1 at screening
  • Radiographically measurable disease by RECIST 1.1

 

Reference:

Study NCT07044336. ClinicalTrials.gov website. 

 

Exclusion criteria

 

The key exclusion criteria are –

  • Uterine sarcomas or uterine neuroendocrine carcinoma
  • Had a recurrence of EC or carcinosarcoma more than >12 months after completing platinum-based therapy administered in the curative-intent setting without any additional platinum-based therapy received in the recurrent setting
  • Previously received treatment with any therapy (approved or investigational) that contained a TOP1i including ADCs
  • Previously received treatment with AZD8205 or another B7-H4 targeting agent
  • History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
  • Active or previously documented autoimmune or inflammatory disorders

Bluestar-Endometrial01 Overview Modal

Bluestar-Endometrial01 trial overview

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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

  • 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.

 

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Bluestar-Endometrial01 trial overview

Tumor
B7-H4-selected advanced/metastatic endometrial cancer

Trial Identifier
NCT07044336

Phase
III

Regimen
Puxitatug samrotecan; doxorubicin/paclitaxel

Visit ct.gov

Study Design

Bluestar-Endometrial01

Inclusion criteria

The key inclusion criteria are –

  • Histologically confirmed diagnosis of EC or carcinosarcoma
  • Recurrent/metastatic EC (with radiological or objective evidence of recurrence or progression)
  • Received prior platinum-based chemotherapy and anti-PD-1/anti- PD-L1 therapy, either separately or in combination
  • ECOG PS of 0 or 1 at screening
  • Radiographically measurable disease by RECIST 1.1

 

Reference:

Study NCT07044336. ClinicalTrials.gov website. 

 

Exclusion criteria

 

The key exclusion criteria are –

  • Uterine sarcomas or uterine neuroendocrine carcinoma
  • Had a recurrence of EC or carcinosarcoma more than >12 months after completing platinum-based therapy administered in the curative-intent setting without any additional platinum-based therapy received in the recurrent setting
  • Previously received treatment with any therapy (approved or investigational) that contained a TOP1i including ADCs
  • Previously received treatment with AZD8205 or another B7-H4 targeting agent
  • History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
  • Active or previously documented autoimmune or inflammatory disorders

Bluestar-Endometrial01 Overview Modal

Bluestar-Endometrial01 trial overview

Take me to ClinicalTrials.Gov

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Abbreviations

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  • DNA

    deoxyribonucleic acid

  • IgG1

    immunoglobulin G1

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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