Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer

NCT ID: NCT05367440

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-02
• Study Completion Date: 2031-04-11

Brief Summary

This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD5305 when given in combination with new hormonal agents (NHAs) in patients with Metastatic Prostate Cancer.

Detailed Description

The study consists of 2 parts, Part A and Part B. Part A consists of the dose escalation cohorts and will include patients with metastatic castration resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer (mCSPC); Part B consists of dose expansion cohorts and will include patients with mCSPC only.

Part A comprises 4 individual arms each evaluating the safety, tolerability, and preliminary efficacy of AZD5305 in combination with a specific new hormonal agent (NHA). Part B comprises up to 4 individual arms (arms to be opened at Sponsor's discretion) each investigating the preliminary efficacy and aims to further build on the safety data for the combination of AZD5305 with a specific NHA.

Approximately 783 patients will be enrolled and screened to ensure the required number of evaluable patients in each part and arm are enrolled. For Part A, 356 patients may be screened to obtain up to approximately 308 patients that can be assigned to study treatments across all study arms (1 to 4). For Part B dose expansion cohorts, up to 427 patients may be screened to obtain up to approximately 360 patients that can be assigned to study treatments across all study arms (1 to 4).

Study treatment administration will continue until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 (AZD5305 in combination with enzalutamide)

Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group Type: EXPERIMENTAL

AZD5305

Intervention Type: DRUG

Patients will receive an oral dose of AZD5305 once daily

Enzalutamide

Intervention Type: DRUG

Patients will receive an oral dose of Enzalutamide once daily

Arm 2 (AZD5305 in combination with abiraterone acetate)

Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group Type: EXPERIMENTAL

AZD5305

Intervention Type: DRUG

Patients will receive an oral dose of AZD5305 once daily

Abiraterone Acetate

Intervention Type: DRUG

Patients will receive an oral dose of Abiraterone Acetate once daily

Arm 3 (AZD5305 in combination with darolutamide)

Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group Type: EXPERIMENTAL

AZD5305

Intervention Type: DRUG

Patients will receive an oral dose of AZD5305 once daily

Darolutamide

Intervention Type: DRUG

Patients will receive an oral dose of Darolutamide twice daily

Arm 4 (AZD5305 in combination with apalutamide)

Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group Type: EXPERIMENTAL

Apalutamide

Intervention Type: DRUG

Patients will receive an oral dose of Apalutamide once daily

Interventions

AZD5305

Patients will receive an oral dose of AZD5305 once daily

Intervention Type: DRUG

Enzalutamide

Patients will receive an oral dose of Enzalutamide once daily

Intervention Type: DRUG

Abiraterone Acetate

Patients will receive an oral dose of Abiraterone Acetate once daily

Intervention Type: DRUG

Darolutamide

Patients will receive an oral dose of Darolutamide twice daily

Intervention Type: DRUG

Apalutamide

Patients will receive an oral dose of Apalutamide once daily

Intervention Type: DRUG

Other Intervention Names

Xtandi; Zytiga; Nubeqa; Erleada

Eligibility Criteria

Inclusion Criteria

For whole study:

• Age ≥ 18 at the time of screening.
• Histologically confirmed diagnosis of metastatic prostate cancer.
• Candidate for treatment with enzalutamide, abiraterone acetate, darolutamide or apalutamide with documented current evidence of metastatic prostate cancer.
• Surgically or medically castrated.
• Adequate organ and marrow function.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
• Life expectancy ≥ 16 weeks.
• Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 6 months after the last dose of study treatment .

For Patients Recruited Specifically to tumour Pharmacodynamic Cohorts:

• Patients must have at least 1 tumour suitable for paired biopsies

For Part A:

• Patients with Metastatic Castrate ion-Resistant Prostate Cancer (mCRPC) or Metastatic Castration Sensitive Prostate Cancer (mCSPC).

For Part B:

• Patients must have mCSPC (de novo or recurrent) with a baseline PSA value of ≥ 0.2 ng/mL

Exclusion Criteria

For Part A mCRPC patients only:

• Any previous treatment with a new hormonal agent (NHA), poly (adenosine diphosphateribose) polymerase inhibitor (PARPi), Lutetium prostate-specific membrane antigen (Lu-PSMA), platinum chemotherapy
• Patients recruited to the PDc cohorts should not have received a prior use of new hormonal agents (NHA).

For Part A and Part B mCSPC Patients:

• Any previous treatment with a PARPi, platinum, NHA, Immuno-oncology (IO), radiopharmaceutical therapy, or prior treatment with docetaxel in mCSPC setting.
• Concomitant use of medications or herbal supplements known to be:

1. Strong and moderate CYP3A4 inducers/inhibitors (applies for all arms)

2. For Arm 1 (enzalutamide) patients: Strong CYP2C8 inhibitors

3. For Arm 3 (darolutamide) patients: Strong P-glycoprotein inducers

• Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
• Treatment with any of the following:

1. Any investigational agents or study interventions from a previous clinical study within 5 half lives or 3 weeks (whichever is longer) of the first dose of study treatment.

2. Any other anticancer treatment within the following time periods prior to the first dose of study treatment: (i) Cytotoxic and non-cytotoxic treatment: 3 weeks or 5 half-lives (whichever is shorter). (ii) Biological products including immuno-oncology agents: 4 weeks before enrolment.

3. Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.

• Any concurrent anticancer therapy or concurrent use of prohibited medications.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
• With the exception of alopecia, and peripheral neuropathy; any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of study enrolment.
• Any history of persisting (> 2 weeks) severe pancytopenia.
• Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
• Any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• Patients with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy.
• 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.
• Patients with history of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection.
• Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
• Any condition that would interfere with evaluation of the study treatment or interpretation of patient safety or study results.
• Uncontrolled intercurrent illness within the last 12 months, including but not limited to, active interstitial lung disease, serious chronic gastrointestinal (GI) conditions associated with diarrhoea, or psychiatric illness/social situations
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence.
• 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.
• Arm 1 (Enzalutamide) and Arm 4 (Apalutamide): History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma).
• Arm 2 (Abiraterone acetate) only: (i) Active infection or other medical condition that would contraindicate the use of systemic steroids (prednisone/prednisolone). (ii) Low serum potassium (< 3.5 mmol/L). (iii) History of uncontrolled pituitary or adrenal dysfunction.
• Arm 4 (Apalutamide): (i) Moderate or severe skin conditions or diseases that could affect the skin (eg. scleroderma, lupus). (ii) Any skin or medical condition that in the Investigator's opinion could increase the risk of skin toxicity.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Detroit, Michigan, United States

Research Site

Detroit, Michigan, United States

Research Site

Syracuse, New York, United States

Research Site

Myrtle Beach, South Carolina, United States

Research Site

Houston, Texas, United States

Research Site

Houston, Texas, United States

Research Site

Camperdown, , Australia

Research Site

Darlinghurst, , Australia

Research Site

East Melbourne, , Australia

Research Site

Heidelberg, , Australia

Research Site

Melbourne, , Australia

Research Site

St Leonards, , Australia

Research Site

Candiolo, , Italy

Research Site

Milan, , Italy

Research Site

Orbassano, , Italy

Research Site

Padua, , Italy

Research Site

Cambridge, , United Kingdom

Research Site

Glasgow, , United Kingdom

Research Site

Manchester, , United Kingdom

Research Site

Plymouth, , United Kingdom

Countries

United States; Australia; Italy; United Kingdom

Other Identifiers

2023-508536-64-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-006289-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D9720C00003

Identifier Type: -

Identifier Source: org_study_id