Detailed Description:~This is a Phase 2, open-label, multiple-dose, multiple-arm, parallel assignment study in patients with mCRPC who have progressed after treatment with at least 2 prior lines of anticancer therapy. It will enroll subjects into one of 5 molecularly defined cohorts based on the results of acceptable, documented prior diagnostic testing:~Cohort A: Aggressive variant prostate cancer (AVPCa)~Cohort B: Homologous recombination deficient (HRD)/cyclin-dependent kinase 12 (CDK12) biallelic loss tumors that have progressed on poly-adenosine diphosphate ribose polymerase inhibitors (HRD/CDK12 PARP Progressors)~Cohort C: HRD/CDK12 biallelic loss tumors, naive to PARP inhibitors (HRD/CDK12 PARP Naïve)~Cohort D: Microsatellite instability-high (MSI-H) or mismatch repair deficient (MMRD), or tumor mutational burden-high (TMB-H) tumors~Cohort E: No Targetable Mutations~Subjects will receive vudalimab alone (Cohort D) or in combination with standard therapy: Cohort A - vudalimab + carboplatin + cabazitaxel (or docetaxel if no prior treatment); Cohorts B, and E - vudalimab + cabazitaxel (or docetaxel if no prior treatment), Cohort C - vudalimab + olaparib.
This Phase 2 study will investigate the safety and clinical activity of vudalimab (XmAb20717) alone or in combination with standard of care anticancer therapies in patients with metastatic castration-resistant prostate cancer (mCRPC) who have been treated with at least 2 prior lines of anticancer therapy.