(Title in lay language): A trial to learn how safe AZD0516 is and how well it works with and without other cancer treatments in adults with metastatic prostate cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Mar 2026 → ongoing

Decision date (initial)

2025-12-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-520026-11-00

ClinicalTrials.gov

NCT07181161

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

Dose Escalation (Part A)
Safety
To assess the safety and tolerability and to determine the MTD and/or RDE(s) of AZD0516 as monotherapy and in combination with anti-cancer agents.
Dose Optimisation (Part B)
Efficacy
To assess the preliminary antitumour activity of AZD0516 as monotherapy and in combination with anti-cancer agents.
Dose Optimisation (Part B)
Safety
To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.
Efficacy Expansion (Part C)
Efficacy
To assess the anti-tumour activity of AZD0516 as monotherapy and/or in combination with other anti-cancer agents.

Secondary objectives 5

1. Dose Escalation (Part A), Dose Optimisation (Part B), Efficacy Expansion (Part C) - Efficacy - To assess the preliminary anti-tumour activity of AZD0516 as monotherapy and/or in combination with other anti-cancer agents.
2. Dose Escalation (Part A) and Dose Optimisation (Part B) - Pharmacokinetics - To characterise the PK of AZD0516 when given as monotherapy and in combination with anti-cancer agents.
3. Dose Escalation (Part A) and Dose Optimisation (Part B) - Biomarker - To investigate STEAP2 expression and relationship to response to AZD0516.
4. Dose Escalation (Part A) and Dose Optimisation (Part B) - Immunogenicity - To determine the immunogenicity of AZD0516 as monotherapy and in combination with anti-cancer agents.
5. Efficacy Expansion (Part C) - Safety - To further assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.

Conditions and MedDRA coding

Metastatic Prostate Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Informed Consent - Capable of giving signed informed consent as described in the study protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Informed Consent - Consent to provide adequate baseline tumour sample prior to start of treatment, as applicable per module-specific criteria.
3. Informed Consent - Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional Genomics Initiative research that supports the Genomic Initiative (see study protocol). Participants who do not provide informed consent for Optional Genetic Research may still be enrolled in the study.
4. Age - Participant must be ≥ 18 years of age inclusive, or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the ICF.
5. Tissue sample - Provision of baseline archival or newly obtained FFPE tumour sample is mandatory.
6. Type of Participant and Disease Characteristics - Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the prostate. Focal high grade neuroendocrine features are permitted.
7. Type of Participant and Disease Characteristics - Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within ≤ 28 days before treatment allocation. Ongoing ADT with a 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.
8. Type of Participant and Disease Characteristics - Measurable PSA ≥ 1 µg/L (≥ 1 ng/mL).
9. Type of Participant and Disease Characteristics - Documented current evidence of metastatic prostate cancer, where metastatic status is defined as at least one documented metastatic lesion on either CT/MRI or bone scan. Participants whose disease spread is limited to regional pelvic lymph nodes or local recurrence (eg, bladder, rectum) are not eligible.
10. Type of Participant and Disease Characteristics - ECOG performance status of 0 or 1.
11. Type of Participant and Disease Characteristics - Life expectancy of at least 12 weeks in the opinion of the investigator.
12. Type of Participant and Disease Characteristics - 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 as indicated in the study protocol).
13. Type of Participant and Disease Characteristics - Participants must have received and progressed on, are refractory or are intolerant to standard therapy in accordance with local practice for their stage of disease or, in the opinion of the investigator, a clinical study is the best option for the participant’s next treatment based on response and/or tolerability to prior therapy. Participants with contraindications, to standard of care therapy, may also be considered if it is documented, and they have been informed about all therapeutic options.
14. Sex and Contraceptive/Barrier Requirements - Male, as assigned at birth, inclusive of all gender identities: (a) Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. (b) Participants who are sexually active with a female partner of childbearing potential, including a pregnant partner, must use a male condom (and add spermicide, if available) while on study and for an appropriate period after final dose of study intervention. (i) Investigators are to advise participants about the preservation of sperm prior to AZD0516. (ii) It is strongly recommended for the female partner of a male participant to also use a highly effective method of contraception throughout this period, as described below: Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study interventions [periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception]), a vasectomised partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™, Xulane™, or NuvaRing®.
15. Sex and Contraceptive/Barrier Requirements - Participants must refrain from sperm donation while on study and for an appropriate period following the last dose of study intervention.

Exclusion criteria 24

1. Medical Conditions - 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. Any participant at high risk of cord compression based on imaging at screening should have the bone lesions treated prior to study enrolment. A scan to confirm the absence of brain metastases is not required.
2. Medical Conditions - History of leptomeningeal carcinomatosis.
3. Medical Conditions - Unresolved toxicities of Grade ≥ 2 (NCI CTCAE v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy). Participants with chemotherapy-induced Grade 2 neuropathy may be eligible at discretion of the investigator and after consultation with the AstraZeneca Study Physician.
4. Medical Conditions - Uncontrolled intercurrent illness within the last 12 months, including but not limited to, uncontrolled diabetes mellitus, substance abuse, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of experiencing AEs or compromise the ability of the participant to give written informed consent.
5. Medical Conditions - Cardiovascular disorder defined as: (a) History of arrhythmia (such as multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Note: Abnormalities in serum electrolytes that can increase the risk of arrhythmic events (ie, sodium, potassium, calcium, magnesium) should be corrected before starting the study intervention. (b) Uncontrolled hypertension, defined as systolic BP > 160 mmHg or diastolic BP > 90 mmHg despite optimal medical management, as determined by the investigator. Hypertensive participants may be eligible, but BP must be adequately controlled at baseline. Participants may be re-screened regarding the BP requirement. (c) Symptomatic hypotension at screening. (d) Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months. (e) History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischaemic attack in the last 6 months prior to screening. (f) Symptomatic heart failure (as defined by New York Heart Association class ≥ 2). (g) Prior or current cardiomyopathy. (h) Severe valvular heart disease. (i) Mean resting QTcF > 470 ms obtained from triplicate ECGs and averaged, recorded within 5 minutes. (j) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in a first degree relative.
6. Medical Conditions - History of malignancy, except for: (a) Malignancy treated with curative intent and with no known active disease for at least 2 years before the first dose of study intervention and with low potential risk for recurrence. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease. (d) Localised non-invasive primary disease under surveillance.
7. Medical Conditions - Active infection exclusions, including tuberculosis and infections with HBV (verified by known positive HBsAg result), HCV, or HIV (verified by positive HIV-1 or HIV-2 antibodies). (a) Known uncontrolled hepatitis B and/or chronic or active hepatitis B with HBV DNA ≥ 100 IU/mL, refer to the protocol for screening tests and eligibility algorithm. (i) Participants with HBsAg positive are eligible if HBV DNA < 100 IU/mL and agrees to start or maintain antiviral treatment. (ii) Participants with HBsAg negative and HBV viral load ‘detectable’ are eligible if HBV DNA < 100 IU/mL and agrees to start or maintain antiviral treatment. (iii) Participants with HBsAg negative, anti-HBc positive, and HBV DNA ‘undetectable’ are eligible. (iv) Participants with HBsAg negative, anti-HBc negative, and anti-HBs positive are eligible. (v) Participants with HBsAg positive or HBV DNA detectable should receive antiviral prophylactic therapy for the duration of anti-cancer therapy, as well as for at least 12 months after the last dose of anti-cancer therapy. Participants should have at least 2 weeks of antiviral prophylaxis before starting study drug. Refer to the protocol for additional management guidelines. (b) Known chronic, active, or uncontrolled hepatitis C, defined as anti-HCV IgM/IgG positive and HCV RNA detectable by polymerase chain reaction. Participants with a history of HCV infection are eligible if they have been treated and cured with an undetectable HCV viral load at least 12 weeks post antiviral treatment of HCV.
8. Medical Conditions - Active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
9. Medical Conditions - Any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
10. Medical Conditions - History of non-infectious ILD/pneumonitis that has required oral or intravenous steroids, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening (findings from screening CT/HRCT if available).
11. Medical Conditions - Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior pneumonectomy or require supplemental oxygen (including intermittent or discretionary use).
12. Medical Conditions - Participants with MDS/AML or with features suggestive of MDS/AML.
13. Prior/Concomitant Therapy - Previous treatment with a STEAP2 targeting modality.
14. Prior/Concomitant Therapy - Previous treatment with a chemotherapeutic agent or ADC that inhibits TOP1 activity.
15. Prior/Concomitant Therapy - Any concomitant medications or herbal supplements known to be strong inhibitors of metabolic enzymes. The required washout period prior to starting study intervention is at least 21 days or 5 half-lives, whichever is longer.
16. Prior/Concomitant Therapy - Treatment with any of the following agents and interventions: (a) Any other anti-cancer agents within the following time periods prior to the first dose of study intervention (i) Cytotoxic treatment: 21 days. (ii) Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is longer). (iii) Biological products including immuno-oncology agents: 28 days. (iv) Any investigational agents or study interventions from a previous clinical study: 28 days or 5 half-lives (whichever is longer). (b) Radiotherapy: Participants who have received wide field of radiation (including whole brain radiotherapy) within 28 days prior to the first dose of study intervention or limited field radiotherapy (including stereotactic radiotherapy or gamma-knife) for palliative intent within 14 days prior to the first dose of study intervention. Participants who have not recovered from radiotherapy-related toxicity to Grade 1 or baseline will not be eligible. (c) Major surgery (as defined by the investigator): Within 28 days prior to the first dose of study intervention. (d) Chloroquine/hydroxychloroquine: At least 14 days prior to the first dose of study intervention.
17. Prior/Concomitant Therapy - Any concurrent anti-cancer treatment except for GnRH modulators, which should be continued throughout the study (unless bilateral orchiectomy). Participants on a stable bisphosphonate or denosumab regimen are eligible.
18. Prior/Concomitant Therapy - Any concomitant medications known to prolong QTc and/or have a known risk for TdP should not be combined with AZD0516. The required washout period prior to starting study intervention is at least 7 days or 5 half-lives, whichever is longer. Exception: Anti-emetics known to prolong QTc interval are permitted; ECGs and electrolytes will be closely monitored.
19. Prior/Concomitant Therapy - Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Participants, if enrolled, should not receive live vaccine while receiving study intervention and up to 3 months after the last dose of study intervention. Participants can receive COVID-19 vaccines, at the discretion of the investigator, following a benefit/risk evaluation for the individual participant and in accordance with local rules and regulations and vaccination guidelines. Note: If a COVID-19 vaccine is administered it should be done > 72 hours prior to study intervention initiation or after the completion of the DLT period.
20. Prior/Concurrent Clinical Study Experience - Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
21. Prior/Concurrent Clinical Study Experience - Known hypersensitivity to AZD0516 or any of the excipients of the product.
22. Other Exclusions - Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
23. Other Exclusions - Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
24. Other Exclusions - Previous enrolment and treatment in the present study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Escalation (Part A) - Safety: Incidence of AEs, AESIs, SAEs. Incidence of DLTs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG performance status, and physical examination.
2. Dose Optimisation (Part B) and Efficacy Expansion (Part C) - Efficacy: PSA50 response rate.
3. Dose Optimisation (Part B) - Safety: Incidence of AEs, AESIs, SAEs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG perform.

Secondary endpoints 6

1. Dose Escalation (Part A) Dose Optimisation (Part B) Efficacy Expansion (Part C)-Efficacy-PSA related endpoints: PSA50 response rate(Part A), PSA90 response rate, Time to PSA50 response, Time to PSA90 response, Duration of PSA50 response, Duration of PSA90 response, Durable PSA50 response rate, Durable PSA90 response rate, Time to PSA progression, and PSA over time.
2. Dose Escalation (Part A) Dose Optimisation (Part B) Efficacy Expansion (Part C)-Efficacy:Radiological response endpoints and estimands, assessed by the investigator evaluated according to RECIST v1.1 (soft tissue) and PCWG3 (bone) criteria: ORR, BOR, DoR, DRR, DCR, TTR, percentage change in tumour size, and rPFS. Other efficacy endpoint: OS
3. Dose Escalation (Part A) and Dose Optimisation (Part B) - Pharmacokinetics: Plasma concentration of AZD0516, total antibody (conjugated and unconjugated) and total unconjugated warhead. Plasma PK parameters of AZD0516, total antibody (conjugated and unconjugated) and including but not limited to AUC, Cmax, tmax, clearance, and t1/2, as data allow.
4. Dose Escalation (Part A) and Dose Optimisation (Part B) - Biomarker:Target expression via STEAP2 IHC on treatment versus at baseline (in paired biopsy cohorts). Evaluate association of STEAP2 expression with AZD0516 response.
5. Dose Escalation (Part A) and Dose Optimisation (Part B) - Immunogenicity: Evaluate the number and percentage of participants who develop ADA.
6. Efficacy Expansion (Part C) - Safety:Incidence of AEs, AESIs, SAEs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG performance status, and physical examination.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 6

Locations

3 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications