RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT07181161Sponsor: AstraZenecaLast updated: 2026-06-12

Summary

The main purpose of this study is to assess the safety and tolerability of AZD0516 as monotherapy and/or in combination with other anti-cancer agents for treatment of metastatic prostate cancer.

Detailed description

This is a first-in-human modular, Phase I/IIa, open-label, multi-centre study of AZD0516 in participants with metastatic prostate cancer. The study will consist of individual modules, each evaluating the safety, tolerability, preliminary efficacy, PK, pharmacodynamic, and immunogenicity of AZD0516. Module 1: Evaluates AZD0516 as monotherapy. It may include 3 parts, Part A- Dose Escalation, Part B- Dose Optimisation, and Part C- Efficacy Expansion. Module 2: Evaluates AZD0516 in combination with AZD9574. It may include 2 parts, Part A - Dose Escalation and Part B Dose Optimisation.

Arms & interventions

DrugAZD0516
AZD0516 will be administered via intravenous infusion.
DrugAZD9574
AZD9574 will be administered orally.

Outcome measures

Primary

Module 1 and 2: Parts A and B: Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interests (AESIs)
Part A: To assess the safety and tolerability and to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) of AZD0516 as monotherapy and in combination with anti-cancer agents. Part B: To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Part A: Number of participants with Dose Limiting Toxicities (DLTs)
To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.
Time frame: From Day 1 up to end of DLT period (approximately 21 days)
Module 1: Parts B and C and Module 2: Part B: Percentage of participants with Prostate-Specific Antigen (PSA) 50 response rate
The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result.
Time frame: Up to approximately 2 years

Secondary

Module 1 and 2: Part A: Percentage of participants with PSA50 response rate
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Percentage of participants with PSA90 response rate
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Time to PSA 50 response (TTPSA50)
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Time to PSA response (TTPSA90)
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Duration of PSA response 50 (DoPSA50)
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Duration of PSA response 90 (DoPSA90)
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 50 (DRRPSA50)
Time frame: Up approximately 2 years
Module 1 and 2: Parts A, B and C: Percentage of participants with Durable PSA response rate 90 (DRRPSA90)
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Time to PSA Progression (TTPSA)
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Percentage change from baseline in PSA levels
Time frame: Up to approximately 2 years
Module 1 and 2: Parts A, B and C: Percentage of participants with Overall Response Rate (ORR)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Percentage of participants with Best Overall Response (BOR)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Duration of Response (DoR)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Percentage of participants with Durable Response Rate (DRR)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Percentage of participants with Disease Control Rate (DCR)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Time to Response (TTR)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Percentage Change in Tumour Size
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Radiographic Progression-free Survival (rPFS)
Time frame: Up to approximately 3 years
Module 1 and 2: Parts A, B and C: Overall Survival (OS)
Time frame: Up to approximately 3 years
Module 1 and 2: Part A and B: Changes in Plasma concentration of AZD0516
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Area under concentration-time curve (AUC)
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Maximum observed drug concentration (Cmax)
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Time to reach maximum observed concentration (tmax)
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Tobal Body Clearance (CL)
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Half-life (t1/2)
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Plasma concentration of total antibody (conjugated and unconjugated)
Time frame: From Day 1 up to approximately 3 years
Module 1 and 2: Parts A and B: Plasma concentration of total unconjugated payload
Time frame: From baseline up to approximately 3 years
Module 1 and 2: Parts A and B: Change from baseline in STEAP2 tumour expression
Time frame: From baseline up to approximately 3 years
Module 1 and 2: Parts A and B: Association of STEAP2 expression with AZD0516 response
Time frame: From baseline up to approximately 3 years
Module 1 and 2: Parts A and B: Number of participants with positive antidrug antibodies (ADAs)
Time frame: Up to approximately 3 years
Module 1: Part C: Number of participants with AEs, SAEs and AESIs
Time frame: From Day 1 up to approximately 3 years

Eligibility criteria

Sex: MaleAge: 18 Years to 130 YearsHealthy volunteers: No

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.

Study locations (11)

Research Site

Fayetteville, Arkansas, 72703

Recruiting

Research Site

Los Angeles, California, 90095

Recruiting

Research Site

Towson, Maryland, 21204

Suspended

Research Site

Boston, Massachusetts, 02114

Recruiting

Research Site

Ann Arbor, Michigan, 48109

Recruiting

Research Site

Detroit, Michigan, 48201

Recruiting

Research Site

Buffalo, New York, 14263

Suspended

Research Site

New York, New York, 10065

Recruiting

Research Site

Providence, Rhode Island, 02906

Recruiting

Research Site

Myrtle Beach, South Carolina, 29572

Recruiting

Research Site

Houston, Texas, 77030

Recruiting