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PSMA radioconjugate

Compound (225Ac) zadavotide guraxetan (AZD2265)

Area under investigation

mCRPC

Scientific PillarRadioconjugates

 

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AlphaBreak trial overview

Tumor

PSMA-positive mCRPC

Trial Identifier

NCT06402331

Phase

II

Regimen

(225Ac) zadavotide guraxetan monotherapy, IV administration

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This study is sponsored by Fusion Pharmaceuticals Inc.

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Target Overview

Prostate-Specific Membrane Antigen (PSMA) is a type II transmembrane glycoprotein that is present in all prostatic tissues and is overexpressed in prostate cancer cells.1 It is a glutamate carboxypeptidase II enzyme and encoded by the human FOLH1 (folate hydrolase 1) gene. PSMA expression is associated with disease progression and worse clinical outcomes.2,3,4

Compound Overview

Actinium (225Ac) zadavotide guraxetan (AZD2265) is a PSMA targeting radioconjugate (also known as 225Ac-PSMA-I&T) designed for metastatic castration-resistant prostate cancer. It consists of three parts: 1) a moiety that binds to PSMA, 2) a linker, and 3) a chelator that acts as a “cage” to hold radioactive isotopes, like actinium-225. PSMA-I&T was optimized for high PSMA affinity, fast pharmacokinetics, and high metabolic stability as described in Weineisen et al.5

(225Ac) Zadavotide guraxetan binds with high affinity to PSMA on the surface of prostate cancer cells. The radioactive decay of actinium-225 (and subsequent daughter isotopes) leads to alpha particle emission, which results in significant DNA and cellular damage and apoptotic cell death. 

Mechanism of Action

  • Mechanism of Action

References

1. Chang SS. Rev Urol. 2004;6 Suppl 10(Suppl 10):S13-S18. 2. Minner S, Wittmer C, Graefen M, et al. Prostate. 2011;71(3):281–288. 3. Vlachostergios PJ et al. Front Oncol. 2021;11:630589. 4. Hupe MC, Philippi C, Roth D, et al. Front Oncol. 2018;8:623. 5. Weineisen M et al. J Nucl Med. 2015;56(8):1169-1176.

 

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AlphaBreak trial overview

Tumor

PSMA-positive mCRPC

Trial Identifier

NCT06402331

Phase

II

Regimen

(225Ac) zadavotide guraxetan monotherapy, IV administration

Visit ct.gov

This study is sponsored by Fusion Pharmaceuticals Inc.

AlphaBreak Overview Modal

AlphaBreak trial overview

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Abbreviations

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  • Ac

    actinium

  • FOLH1

    folate hydrolase 1

  • I&T

    Imaging & Therapy

  • mCRPC

    metastatic castration-resistant prostate cancer

  • PSMA

    prostate-specific membrane antigen

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