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PSMA radioconjugate

Compound (225Ac) zadavotide guraxetan (AZD2265)

Area under investigation

mCRPC

Scientific PillarRadioconjugates

 

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VECTRA-01 trial overview

Tumor

PSMA-positive metastatic castration-resistant prostate cancer

Trial Identifier

NCT07611110

Phase

III

Regimen

(225Ac) zadavotide guraxetan; active comparator: investigator's choice of cabazitaxel, abiraterone, enzalutamide, apalutamide, darolutamide, rezvilutamide, radium-223

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Study Design

Inclusion criteria

The key inclusion criteria are –

  • ≥ 18 years of age
  • Diagnosis of adenocarcinoma of prostate
  • Prior orchiectomy and/or ongoing ADT and a castrate level of plasma/serum testosterone
  • Progressive mCRPC following the most recent treatment at the time of study entry, with at least 1 metastatic lesion (measurable and/or non-measurable) that is suitable for repeated assessment by CT and/or MRI and/or bone scan
  • Previously treated with at least 2 cycles of PSMA-directed β-emitting radioconjugate
  • Previously treated with at least 1 ARPI (eg, enzalutamide, abiraterone, etc.) or taxane-based chemotherapy regimen for either mHSPC or CRPC
  • Positive PSMA PET/CT scans, obtained with PSMA ligands (⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL)
  • ECOG PS of 0 to 2
  • Adequate organ and bone marrow function as described in study protocol
  • Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention
  • Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners

 

Reference:

Study NCT07611110. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are –

  • Prior treatment with an α-emitting molecular targeted therapeutic radioconjugate (prior treatment with radium-223 is permitted)
  • Progression on PSMA-directed β-emitting radioconjugate prior to the administration of Cycle 3
  • Receipt of > 6 cycles of PSMA-directed β-emitting therapeutic RC
  • History of another primary malignancy, with exceptions
  • Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, with exceptions
  • Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention
  • Clinically significant ECG abnormalities, with exceptions

EvoPAR-Prostate02 Overview Modal

VECTRA-01 trial overview

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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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VECTRA-01 trial overview

Tumor

PSMA-positive metastatic castration-resistant prostate cancer

Trial Identifier

NCT07611110

Phase

III

Regimen

(225Ac) zadavotide guraxetan; active comparator: investigator's choice of cabazitaxel, abiraterone, enzalutamide, apalutamide, darolutamide, rezvilutamide, radium-223

Visit ct.gov

Study Design

Inclusion criteria

The key inclusion criteria are –

  • ≥ 18 years of age
  • Diagnosis of adenocarcinoma of prostate
  • Prior orchiectomy and/or ongoing ADT and a castrate level of plasma/serum testosterone
  • Progressive mCRPC following the most recent treatment at the time of study entry, with at least 1 metastatic lesion (measurable and/or non-measurable) that is suitable for repeated assessment by CT and/or MRI and/or bone scan
  • Previously treated with at least 2 cycles of PSMA-directed β-emitting radioconjugate
  • Previously treated with at least 1 ARPI (eg, enzalutamide, abiraterone, etc.) or taxane-based chemotherapy regimen for either mHSPC or CRPC
  • Positive PSMA PET/CT scans, obtained with PSMA ligands (⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL)
  • ECOG PS of 0 to 2
  • Adequate organ and bone marrow function as described in study protocol
  • Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention
  • Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners

 

Reference:

Study NCT07611110. ClinicalTrials.gov website.

Exclusion criteria

The key exclusion criteria are –

  • Prior treatment with an α-emitting molecular targeted therapeutic radioconjugate (prior treatment with radium-223 is permitted)
  • Progression on PSMA-directed β-emitting radioconjugate prior to the administration of Cycle 3
  • Receipt of > 6 cycles of PSMA-directed β-emitting therapeutic RC
  • History of another primary malignancy, with exceptions
  • Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, with exceptions
  • Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention
  • Clinically significant ECG abnormalities, with exceptions

EvoPAR-Prostate02 Overview Modal

VECTRA-01 trial overview

Take me to ClinicalTrials.Gov

You are now leaving the AstraZeneca Oncology Portfolio.
You have selected a link that will take you to a site maintained by a third party.

Click ‘Cancel’ to return back or ‘Continue’ to proceed.

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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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