AZD5305 vs Placebo in Men with Metastatic Castration Sensitive Prostate Cancer Receiving Physicians Choice New Hormonal Agents

Phase 3

Conditions: Health Condition 1: C61- Malignant neoplasm of prostate

Registration Number: CTRI/2024/06/068435

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Yet Recruiting

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

Inclusion criteria

Type of Participant and Disease Characteristics

1Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.

2Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or 1 soft tissue lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment with CT and/or MRI. Participants with metastatic disease identified by PSMA-PET only, will not be eligible. Participants with disease limited to regional pelvic lymph nodes only are not eligible.

3Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting 14 days and 4 months prior to randomisation with no radiographic evidence of disease progression or rising PSA levels prior to first day of dosing. Participant must remain on ADT throughout the study and be a candidate for treatment with an NHA. Combination with first generation AR antagonists to counter testosterone flare is permitted until randomisation.

Note: Due to the interaction between relugolix and enzalutamide, this combination of ADT and NHA is not allowed. Relugolix is otherwise permitted.

4ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.

5Minimum life expectancy of 6 months.

6Provision of a FFPE tumour tissue sample and a blood sample for ctDNA as specified in the Laboratory Manual refer to Section 8.8 and to Table 7.

7Confirmed HRRm status by central tumour tissue and/or ctDNA test is required to determine cohort eligibility as described below:

(a)Participants will be considered eligible for the HRRm Cohort if a loss of function mutation (deleterious/pathogenic or suspected deleterious/likely pathogenic in at least one of the genes BRCA1, BRCA2, ATM, CDK12, PALB2, RAD51B, RAD51C, RAD51D, and BARD1) is detected by either central tumour tissue or central ctDNA test, ie, a positive HRRm result reported by one assay (tissue or ctDNA) is sufficient irrespective of the result of the other assay.

(b) Participants will be considered eligible for the Non-HRRm Cohort if no gene mutation (in any of BRCA1, BRCA2, ATM, CDK12, PALB2, RAD51B, RAD51C, RAD51D, and BARD1) is detected by either tumour tissue or ctDNA test and a participant must have a non-HRRm tumour tissue test result. Participants without a valid non-HRRm tumour tissue result will not be eligible for randomisation into the Non-HRRm Cohort. For details see Table 7.

Exclusion Criteria

Exclusion criteria

Medical Conditions

1Participants with a history of MDS AML or with features suggestive of MDS AML as determined by prior diagnostic investigation. Specific screening for MDS AML is not required.

2Participants with any known predisposition to bleeding eg, active peptic ulceration, recent within 6 months haemorrhagic stroke, proliferative diabetic retinopathy.

3Any history of persisting 2 weeks severe cytopenia due to any cause eg, absolute neutrophil count 0.5 109 L or platelets 50 109 L

4Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.

5History of another primary malignancy, with the following exceptions:

Adequately resected non-melanoma skin cancer.

Curatively treated in situ disease.

Malignancy treated with curative intent 3 years before the first dose of study intervention, and with no known active disease during the intervening time period.

6Persistent toxicities CTCAE Grade 2 caused by previous anticancer therapy. Participants with side effects that are not reasonably expected to affect the safety of the participant on study intervention in the opinion of the investigator eg, ADT-related side effects may be included if agreed with the Study Clinical Lead

7Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and signing the main study ICF.

8Any of the following cardiac criteria:

Mean resting corrected QT interval QTcF 470 milliseconds obtained from triplicate ECGs and averaged, recorded 5 minutes apart.

Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.

9History of arrhythmia multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, which is symptomatic or requires treatment CTCAE Grade 3, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the AstraZeneca study physician

10Other cardiovascular disease as defined by any of the following:

Symptomatic heart failure as defined by New York Heart Association class 2.

Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention or coronary artery bypass grafting within 6 months prior to randomisation.

Cardiomyopathy of any aetiology

Presence of clinically significant valvular heart disease.

Left ventricular ejection fraction 50% measured by echocardiogram or MUGA scan at screening or based on assessment performed within 6 months prior to randomisation.

Transient ischaemic attack, or stroke within 6 months prior to randomisation.

Participants with symptomatic hypotension at screening.

Uncontrolled hypertension despite medical management.

11Evidence of active and uncontrolled hepatitis B and/or hepatitis C. Screeni

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
(BRCAm and Non HRRm cohort) <br/ ><br>Radiographic progression-free survival (rPFS) in participants with mCSPC <br/ ><br>Timepoint: RECIST 1.1 is to be assessment at screening, and Every 16 weeks (± 14 days) from randomisation until RECIST 1.1 and/or PCWG3-defined radiographic PD. <br/ ><br>rPFS is defined as the time from randomisation to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or, death due to any cause. <br/ ><br> <br/ ><br>

Secondary Outcome Measures