PRIMARY OBJECTIVE:~I. To evaluate the response rate of tuvusertib (ATR inhibitor M1774) in highly refractory prostate cancer.~SECONDARY OBJECTIVES:~I. To evaluate the overall survival (OS) of refractory SPOP-mutant prostate cancer patients receiving tuvusertib (M1774).~II. To evaluate the progression-free survival (PFS) of refractory SPOP-mutant prostate cancer patients receiving M1774.~III. To evaluate the Common Terminology Criteria for Adverse Events (CTCAE) 5.0-defined adverse event (AE) rates of refractory SPOP-mutant prostate cancer patients receiving M1774.~EXPLORATORY OBJECTIVE:~I. To determine changes in SPOP-mutant circulating tumor deoxyribonucleic acid (ctDNA) and SPOP-, ATR-, and ATM-related gene signature changes on ATR inhibition, including RAC1, FDFT1, DHCR24, DHCR7, and MVD.~OUTLINE:~Patients receive tuvusertib orally (PO) on study. Patients also undergo biopsy, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET)/MRI, PET/CT or ultrasound (U/S) and collection of blood samples throughout the trial.~After completion of study treatment, patients are followed up every 6 months for 2 years.
This phase II trial tests how well M1774 works in treating patients with prostate cancer that does not respond to treatment (refractory) and who have a mutation in the speckle type BTB/POZ protein (SPOP) gene. M1774 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.