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AZD0516 alone and with AZD9574 for metastatic prostate cancer

A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0516 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Metastatic Prostate Cancer

Phase1; Phase2 Interventional AstraZeneca · NCT07181161

This trial will test AZD0516, alone and combined with AZD9574, to see if it is safe and helps people with metastatic prostate cancer who have castrate-level testosterone.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment177 (estimated)
Ages18 Years to 130 Years
SexMale
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsprednisone
Locations52 sites (Fayetteville, Arkansas and 51 other locations)
Trial IDNCT07181161 on ClinicalTrials.gov

What this trial studies

This first-in-human, modular Phase I/IIa open-label study will enroll participants with metastatic prostate adenocarcinoma to test AZD0516 as monotherapy and in combination with AZD9574. The protocol includes dose-escalation, dose-optimization, and efficacy expansion parts to define safety, tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity. Mandatory archival or new FFPE tumor samples will be collected for biomarker analyses, and participants must have castrate-level testosterone and measurable PSA. The multi-centre design allows sequential evaluation of monotherapy (Module 1) followed by combination dosing with AZD9574 (Module 2).

Who should consider this trial

Good fit: Ideal candidates are people with histologically confirmed metastatic prostate adenocarcinoma on continuous androgen deprivation with castrate testosterone levels, measurable PSA (≥1 ng/mL), ECOG 0–1, adequate organ function, and willing to provide a tumour tissue sample.

Not a fit: Patients with poor performance status, inadequate organ or marrow function, non-metastatic disease, inability to provide a required tumour sample, or who are not maintained at castrate-level androgen suppression are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, AZD0516 could provide a new targeted treatment option that improves tumor control or delays progression in metastatic prostate cancer.

How similar studies have performed: Antibody–drug conjugates and other targeted agents have shown activity in metastatic prostate cancer in other programs, but AZD0516 is first-in-human and anti-STEAP2 targeting is a relatively novel approach with limited clinical data.

Eligibility criteria

Show full inclusion / exclusion criteria 
Main Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the prostate. Focal high grade neuroendocrine features are permitted.
* Measurable PSA ≥ 1 μg/L (≥ 1 ng/mL).
* Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within ≤ 28 days before treatment allocation. Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) modulator for participants who have not undergone bilateral orchiectomy must be initiated at least 2 weeks prior to consent and must continue throughout the study.
* Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
* Adequate organ and marrow function in the absence of blood transfusion or growth factor support (within 21 days prior to the scheduled first dose of study intervention).
* Provision of baseline archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumour sample is mandatory.
* Documented current evidence of metastatic prostate cancer
* Life expectancy of at least 12 weeks in the opinion of the investigator
* Documented mCRPC progression at screening as assessed by the investigator with at least one of the following criteria:

  1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the screening visit should be ≥ 1 μg/L (1 ng/mL).
  2. Radiographic disease progression in soft tissue based on response evaluation criteria in solid tumors (RECIST) v1.1 criteria with or without PSA progression as per prostate cancer working group 3 (PCWG3).
  3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on a bone scan as per PCWG3 with or without PSA progression.

Main Exclusion Criteria:

* Cancer related spinal cord compression, or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of \> 10 mg prednisone/day or equivalent for at least 4 weeks prior to study enrolment.
* History of leptomeningeal carcinomatosis.
* Unresolved toxicities of Grade ≥ 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy).
* Uncontrolled intercurrent illness within the last 12 months.
* Cardiovascular disorder (History of arrhythmia, uncontrolled hypertension, symptomatic hypotension, history of brain perfusion problems, symptomatic heart failure, prior or current cardiomyopathy, severe valvular heart disease)
* History of malignancy
* History of non-infectious interstitial lung disease (ILD)/pneumonitis
* Active infection exclusions, including tuberculosis and infections with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV).
* Any known predisposition to bleeding
* Clinically severe pulmonary compromise
* Participants with Myelodysplastic syndrome (MDS)/Acute Myeloid Leukemia (AML) or with features suggestive of MDS/AML.
* Previous treatment with a STEAP2 targeting modality, chemotherapeutic agent that inhibits topoisomerase activity or metabolic enzymes.

Where this trial is running

Fayetteville, Arkansas and 51 other locations

+2 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Prostate CancerMetastatic Castration-Resistant Prostate CancerDose escalation studyAnti-cancer agentsAntibody-drug conjugateAnti-Six-transmembrane epithelial antigen of the prostate 2Metastatic castration resistant prostate cancerAZD0516
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.