EvoPAR‑Prostate05 Phase 3 Trial: Saruparib Maintenance for Metastatic Hormone‑Sensitive Prostate Cancer

EvoPAR‑Prostate05 is a Phase 3 maintenance trial testing the PARP1‑selective inhibitor saruparib (AZD5305) in men with metastatic hormone‑sensitive prostate cancer (mHSPC).The trial enrolls both HRR‑mutated and non‑HRR‑mutated patients but requires that each participant has confirmed homologous recombination repair mutation status (HRRm – genes such as BRCA1, BRCA2, ATM, PALB2, CDK12, RAD51B/C/D, or BARD1), homologous recombination deficiency (HRD) status, and PTEN status at baseline, based on FFPE tumor tissue and circulating DNA, so that outcomes can be analyzed in biologically defined subgroups rather than restricting eligibility to a single genomic class.
These men must have documented metastatic disease before starting first‑line treatment and have completed an intensive upfront regimen with either docetaxel chemotherapy or PSMA‑directed 177Lu radioligand therapy, without evidence of radiographic progression at the end of that course. After this initial therapy, all participants continue on standard androgen deprivation therapy together with an androgen receptor pathway inhibitor (ARPI), typically abiraterone, enzalutamide, or darolutamide, but they are only eligible for the trial if their PSA remains at or above 0.2 ng/mL, a marker of residual biochemical disease despite clinical response.

In this setting, the trial asks whether adding saruparib can prolong disease control compared with continuing ARPI alone. Approximately 1,330 men will be randomized in a double‑blind, placebo‑controlled fashion to receive either saruparib plus their physician’s choice of ARPI or placebo plus the same ARPI, on a background of ongoing medical castration. Saruparib is an oral, next‑generation PARP inhibitor designed to selectively inhibit and trap PARP1, thereby exploiting synthetic lethality in while potentially reducing off‑target effects seen with less selective PARP1/2 agents. The primary endpoint is radiographic progression‑free survival, capturing the time to imaging‑defined progression or death and assessed over roughly 4–5 years of follow‑up, while key secondary endpoints include overall survival, time to subsequent therapy, development of castration resistance, and patient‑reported outcomes related to pain, physical function, and quality of life.

By focusing on men who have already tolerated and responded to intensive early treatment but retain measurable PSA, EvoPAR‑Prostate05 is positioned at the intersection of precision oncology and early intensification in prostate cancer.

Clinical trial.