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

NCT07336446 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D7270C00001
• Study Type: interventional
• Target: 300
• Locations: 8 countries
• Sites: 18

Brief Summary

ANDROMEDA is a first-in-human, Phase I/II, open-label, multicenter study of AZD9750 in participants with metastatic prostate cancer. The trial evaluates safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of AZD9750 as monotherapy and in combination with saruparib.

Conditions

Prostate Cancer

Keywords

Metastasic Prostate Cancer; Prostate Cancer; Androgen Receptor; Proteolysis-targeting chimeras (PROTACs)

Outcome Measures

Primary Outcomes (9)

• Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only)

  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. A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness.

  From first dose of study intervention to 28 days post first dose

• Number of participants with Adverse Events and Serious Adverse Events

  The number of participants with adverse events and with serious adverse events will be assessed.

  From first dose of study intervention up to 37 days after the last dose of study treatment

• Number of participants with Adverse Events leading to discontinuation of study intervention

  The number of participants with clinically significant changes from baseline in vital signs will be assessed.

  From first dose of study intervention up to 37 days after the last dose of study treatment

• Clinically significant changes from baseline in vital signs.

  The number of participants with clinically significant changes from baseline in vital signs will be assessed.

  From first study dose up to 37 days after the last dose of study treatment

• Clinically significant changes from baseline in physical examination.

  The number of participants with clinically significant changes from baseline in physical examination will be assessed.

  From first dose of study intervention up to 37 days after the last dose of study treatment

• Clinically significant changes from baseline in ECOG PS.

  The number of participants with clinically significant changes from baseline in ECOG PS will be assessed.

  From first dose of study intervention up to 37 days after the last dose of study treatment

• Clinically significant changes from baseline in ECGs.

  The number of participants with clinically significant changes from baseline in ECGs will be assessed.

  From first dose of study intervention up to 37 days after the last dose of study treatment

• Clinically significant changes from baseline in laboratory parameters.

  The number of participants with clinically significant changes from baseline in laboratory parameters will be assessed.

  From first dose of study intervention up to 37 days after the last dose of study treatment

• Proportion of participants achieving a ≥50% decrease in PSA from baseline (PSA50) (Part B only)

  To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents in participants with mCRPC.

  From first dose of study intervention up to 14 days after the last dose of study treatment

Secondary Outcomes (14)

• Proportion of participants achieving a ≥ 50% decrease in PSA from baseline (PSA50) (Part A only)

  From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment

• Proportion of participants achieving a ≥ 90% decrease in PSA from baseline (PSA90)

  From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment

• Objective response rate (ORR)

  From randomisation or first dose of study intervention to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months

• Duration of response (DoR)

  From randomisation or first dose of study intervention to the date of first documented radiological disease progression, assessed up to 60 months

• Time to response (TTR)

  From randomisation or first dose of study intervention to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months

Study Arms (7)

Module 1 / Part A1

EXPERIMENTAL

AZD9750 Monotherapy (Dose Escalation) - No randomization

Drug: AZD9750

Module 1 / Part A2

EXPERIMENTAL

AZD9750 Monotherapy (Backfills) - No randomization

Drug: AZD9750

Module 1 / Part B1

EXPERIMENTAL

AZD9750 Monotherapy (Dose Optimization) - Randomization

Drug: AZD9750

Module 1 Part B2

EXPERIMENTAL

AZD9750 Monotherapy (Dose Expansion) - No randomization

Drug: AZD9750

Module 1 / Part B3

EXPERIMENTAL

AZD9750 Monotherapy (Dose Expansion) - No randomization

Drug: AZD9750

Module 2 / Part A

EXPERIMENTAL

AZD9750 + Saruparib (Combination Dose Finding) - No Randomization

Drug: AZD9750; Drug: AZD5305

Module 2/ Part B

EXPERIMENTAL

AZD9750 + Saruparib (Combination Dose Expansion) - No Randomization

Drug: AZD9750; Drug: AZD5305

Interventions

AZD9750 DRUG

AR-PROTAC

Module 1 / Part A1; Module 1 / Part A2; Module 1 / Part B1; Module 1 / Part B3; Module 1 Part B2; Module 2 / Part A; Module 2/ Part B

AZD5305 DRUG

PARP1-selective inhibitor

Also known as: Saruparib

Module 2 / Part A; Module 2/ Part B

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male, as assigned at birth, inclusive of all gender identities
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥18 years or the legal age at the time of signing the informed consent form.
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
• Documented metastatic disease.
• Serum testosterone levels ≤ 50 ng/dL.
• Evidence of disease progression with one of the following:
• PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination.
• Radiographic progression of soft tissue disease by RECIST v1.1 with or without PSA progression.
• Radiographic progression of bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
• ECOG performance status score of 0 or 1.
• Adequate bone marrow and organ function.
• Part A (Module 1)
• (a) Part A1 dose escalation: at least 1 prior ARPI and, if applicable, at least 1 taxane-based chemotherapy (regardless of whether in HSPC or CRPC setting).
• (b) Part A2 backfill: at least 1 but no more than 2 prior ARPIs and, if applicable, at least 1 but no more than 2 prior taxane-based chemotherapies (regardless of whether in HSPC or CRPC setting).
• Part B (Module 1)
• (a) B1/B2 dose optimization/expansion: at least 1 but no more than 2 prior ARPIs and, if applicable, at least 1 but no more than 2 prior taxane-based chemotherapies (regardless of whether in HSPC or CRPC setting).

You may not qualify if:

• Participants with pathological finding consistent with any presence of small cell carcinoma, predominant neuroendocrine carcinoma, or any predominant histology other than prostate adenocarcinoma.
• Brain metastases, or spinal cord compression.
• Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
• Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
• Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism of AZD9750 and relevant combination IMPs.
• Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent \[within 6 months\] hemorrhagic stroke, proliferative diabetic retinopathy).
• Prior treatment with an AR-PROTAC.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (18)

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

San Francisco, California, 94143, United States

NOT YET RECRUITING

Research Site

Tampa, Florida, 33612, United States

NOT YET RECRUITING

Research Site

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Research Site

St Louis, Missouri, 63108, United States

NOT YET RECRUITING

Research Site

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Research Site

Nashville, Tennessee, 37203, United States

RECRUITING

Research Site

Salt Lake City, Utah, 84112, United States

NOT YET RECRUITING

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Calgary, Alberta, T2N 5G2, Canada

NOT YET RECRUITING

Research Site

Vancouver, British Columbia, V5Z 1H7, Canada

NOT YET RECRUITING

Research Site

Chengdu, 610041, China

NOT YET RECRUITING

Research Site

Chūōku, 104-0045, Japan

NOT YET RECRUITING

Research Site

Kashiwa, 227-8577, Japan

RECRUITING

Research Site

Amsterdam, 1066CX, Netherlands

NOT YET RECRUITING

Research Site

Rotterdam, 3015 GD, Netherlands

NOT YET RECRUITING

Research Site

Barcelona, 8035, Spain

NOT YET RECRUITING

Research Site

Cambridge, CB2 2QQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

AZD5305

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: First-in-human, modular, open-label, Phase I/II study with sequential assignment across modules and parts: Part A (monotherapy dose escalation or combination dose finding) and Part B (dose optimization and expansion), evaluating AZD9750 as monotherapy and in combination with saruparib in participants with metastatic prostate cancer.

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 13, 2026
• Study Start: January 27, 2026
• Primary Completion (Estimated): January 26, 2029
• Study Completion (Estimated): January 26, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

CN (1); NL (2); ES (1); GB (1); AU (1); US (8); CA (2); JP (2)