A Randomized, 2-cohort, Double-blind, Placebo-controlled, Phase III Study of AZD5305 in Combination with Physician’s Choice New Hormonal Agents in Patients with HRRm and non-HRRm Metastatic Castration-Sensitive Prostate Cancer (EvoPAR-Prostate01) (AZD5305 Ph3 Prostate)

Research summary

This is a Phase III double-blind, randomised, placebo-controlled, adaptive design study, to assess whether the addition of AZD5305 to physician’s choice NHA improves treatment outcomes of patients in the setting of mCSPC. A schema summarising the key elements of the study design is shown in Figure 1. A total of 1200 participants will be randomised (in a 1:1 ratio) to receive either AZD5305 (600 participants) or matching placebo (600 participants), in combination with physician’s choice of NHA (abiraterone, darolutamide, or enzalutamide) on a background of ADT. The randomisation scheme will be stratified on the following factors: • HRRm/BRCAm status: Prospective FFPE tumour tissue and peripheral blood ctDNA testing will be needed from participants and used for stratification; • Volume of disease per investigator (high vs. low) according to CHAARTED criteria* o *High volume is defined as the presence of visceral metastases and / or ≥ 4 bone metastases with ≥ 1 metastasis beyond the pelvis and vertebral column; • Physician’s choice NHA: o Abiraterone o Darolutamide o Enzalutamide. The study will have an adaptive design, with two interim analyses (interim analysis 1 for futility and interim analysis 2 for sample size re-estimation and adaptive enrichment). Prior to randomization, an FFPE tumour tissue sample from the participant as well as a peripheral blood sample for ctDNA will need to be submitted for prospective testing of HRRm/BRCAm status. The participant will be stratified based on the results from those tests, and treatment on study can be initiated only after test results are available. Participants with a tissue test result of ‘unknown’ will be eligible, up until the moment a cap on the ‘unknown’ stratum is reached. Treatment with ADT can be commenced whilst awaiting biomarker test results, so long as participants are randomized within 4 months. Response evaluation criteria in solid tumours (RECIST) tumour assessments (computed tomography/magnetic resonance imaging) and Prostate Cancer Working Group-3 (PCWG3) assessments (bone scan) will be performed in cycle 3, 5 and every 16 weeks (± 14 days) thereafter until investigator-assessed disease progression by RECIST 1.1 or PCWG-3 bone progression criteria. It is anticipated that the first participant will be enrolled in Quarter 3, 2023. The last subject last visit date is predicted to occur in October 2030. Participants will receive study intervention until investigator-assessed disease progression by RECIST 1.1 or PCWG-3 bone progression criteria, unacceptable toxicity, or the participant requests to stop the treatment.

Principal Investigator

Prof Andrew Protheroe

Contact us

Email: latephaseoncology@ouh.nhs.uk

IRAS number

1008354