A trial to learn how safe AZD9750 is and how well it works in people with metastatic prostate cancer when given with or without other anticancer drugs

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] - Male Urogenital Diseases [C12]

Decision date (initial)

2026-03-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety

Part A and B: To evaluate the safety and tolerability and determine the MTD and/or the RDE(s)/RP2D of AZD9750 as a monotherapy and in combination with other anticancer agents in participants with mCRPC. Part B only: To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents in participants with mCRPC.

Secondary objectives 1

1. For part A and B: To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents and To characterise the PK of AZD9750 as monotherapy and in combination with other anticancer agents.

Conditions and MedDRA coding

Metastatic Prostate Cancer

Study design 4 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant must be ≥ 18 years at the time of signing the informed consent form.
2. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
3. Documented metastatic disease by conventional imaging by clear evidence of at least one bone lesion and/or at least one soft tissue lesion.
4. Surgically or medically castrated, with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before first dose of study intervention.
5. Participants who have had disease progression while undergoing continuous ADT following standard treatment of metastatic prostate cancer, per PCWG3 guidance. (a) PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination. (b) Radiographic progression of soft tissue disease by RECIST v1.1 (Eisenhauer et al 2009) with or without PSA progression. (c) Radiographic progression of bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
6. ECOG performance status score of 0 or 1.
7. Adequate bone marrow and organ function as defined by the protocol.
8. Participant must be male (as assigned at birth), inclusive of all gender identities.
9. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
10. Life expectancy of ≥ 12 weeks.

Exclusion criteria 6

1. Participants with pathological finding consistent with any presence of small cell carcinoma, predominant neuroendocrine carcinoma, or any predominant histology other than prostate adenocarcinoma.
2. Brain metastases, or spinal cord compression.
3. Participants with any of the following cardiac criteria: (a) Mean resting QTcF > 450 milliseconds obtained from triplicate ECGs and averaged, recorded within 5 minutes. (b) Any factors that increase the risk of QTc prolongation such as the congenital long QTc syndrome or family history of long QTc syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QTc interval within 5 half-lives of the first dose of study intervention (see Appendix H 1), as well as factors that increase the risk of arrhythmic events such as uncorrected abnormalities in serum electrolytes (ie, sodium, potassium, calcium, magnesium). (c) Resting heart rate > 90 bpm or < 45 bpm. (d) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, or QRS duration > 120 ms, PR interval > 220 ms, second- or third-degree atrioventricular block), and clinically significant sinus node dysfunction not treated with pacemaker. (e) Baseline LVEF < 50%, or clinically significant diastolic dysfunction/LVEDP increase/pulmonary hypertension.
4. Participants with other cardiovascular diseases as defined by any of the following: (a) Symptomatic heart failure (as defined by New York Heart Association class ≥ 2) or recent hospitalisation for heart failure (< 6 months). (b) Uncontrolled hypertension > 160/90 mmHg. (c) Acute coronary syndrome /acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months, symptomatic angina pectoris. (d) Cardiomyopathy of any aetiology. (e) Presence of clinically significant valvular heart disease. (f) History of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (mean HR < 90 bpm over 24 hours or mean HR < 90 bpm on resting ECG) are permitted. (g) Transient ischaemic attack, or stroke within 6 months prior to screening. (h) Participants with symptomatic hypotension at screening.
5. Unresolved treatment-related toxicities from previous anticancer therapy of CTCAE Grade ≥ 2 (with exception of vitiligo, alopecia).
6. Prior treatment with an AR-PROTAC.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Part A and B (Safety): Incidence of DLTs (Part A)
2. Part A and B (Safety): Incidence of AEs, SAEs
3. Part A and B (Safety): AEs leading to discontinuation of study intervention
4. Part A and B (Safety): Clinically significant changes from baseline in vital signs, physical examination, ECOG PS, ECGs and laboratory parameters.
5. Part B only (Efficacy): Proportion of participants achieving a ≥ 50% decrease in PSA from baseline.

Secondary endpoints 6

1. For Part A and B (Efficacy): Proportion of participants achieving a ≥ 50% decrease in PSA from baseline (Part A).
2. For Part A and B (Efficacy): Proportion of participants achieving a ≥ 90% decrease in PSA from baseline.
3. For Part A and B (Efficacy): ORR, DoR, TTR, rPFS assessed by the Investigator according to RECIST v1.1 (soft tissue) and PCWG3 (bone) criteria.
4. For Part A and B (Efficacy): Best percentage change in TL size from baseline using RECIST v1.1.
5. For Part A and B (Efficacy): Time to PSA response and Time to PSA progression according to PCWG3 criteria.
6. For Part A and B (PK): Plasma concentrations and PK parameters including, but not limited to Cmax, tmax and AUC after oral administration of AZD9750, if data allows.

Investigational products

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

Test 2

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

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 22 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