Deleterious alterations in genes that are directly or indirectly associated with DNA damage repair (DDR) are enriched in lethal aggressive prostate cancer (PC). About 25–30% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor loss-of-function alterations in DDR genes and respond to current androgen receptor (AR) inhibitors.1 Recently, PARP inhibitors (PARPi) have shown promise in mCRPC patients harboring DDR pathway defects, in particular, but not exclusively BRCA2-altered tumors, leading to a breakthrough designation for PARPi by the FDA in this patient population.2,3 Despite responses, resistance is common, and treatment modalities for PARPi-resistant patients are limited.4 Therefore, an urgent unmet need is to develop well-tolerated, targeted combination treatments of PARPi with other agents that create synergy that would allow more durable responses to PARPi and improve the survival of mCRPC patients.