A Safety and Dose-finding Study of PRL-02 Depot in Men With Advanced Prostate Cancer

Inclusion Criteria: * Histological evidence of adenocarcinoma of the prostate * Phase 1a Dose Escalation Groups A and B: participants must have one of the following documented conditions: * mCSPC (must have documentation by positive bone scan \[for bone disease\] or metastatic lesions on computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scan \[for soft tissue\]) * nmCSPC with biochemical relapse of prostate cancer * mCSPC with oligometastatic prostate cancer (e.g., positron emission tomography positive) * mCRPC (must have documentation by positive bone scan \[for bone disease\] or metastatic lesions on CT or MRI scan \[for soft tissue\]) * NOTE: For participants in the Dose Escalation Cohorts (including backfill) at each of the dose levels up to approximately 10 participants with ARPI-naïve mCRPC who have not received prior treatment with an ARPI (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide) will be enrolled. * Phase 1a Dose Escalation Groups A and B: participants with mCRPC must have evidence of disease progression defined as one or more of the following: * Evidence of radiographic progression of disease following the most recent prostate cancer treatment, defined as progressive disease on CT/MRI per RECIST v1.1 or on a bone scan per PCWG3. * PSA progression defined as the following: * PSA nadir is defined as the lowest PSA during or after the most recent treatment. PSA progression is defined as an increased PSA of at least 25% and ≥1 ng/mL above the nadir confirmed by at least 2 measurements with a minimum of 1 week apart, and with at least 1 of the measurements within 90 days prior to screening. * Participants with nmCSPC and biochemical recurrence, who had a radical prostatectomy (with or without radiotherapy) as the primary treatment for prostate cancer, must have a screening PSA ≥1 ng/mL. Participants with nmCSPC and biochemical recurrence who had radiotherapy only, as primary treatment for prostate cancer, must have a screening PSA ≥2 ng/mL above the nadir. * Phase 1b Expansion Groups D and E: participants must have mCRPC Participants in Group D must have received prior treatment with abiraterone acetate, but must not have received treatment with other ARPIs (enzalutamide, apalutamide or darolutamide). Participants in Group E must have received prior treatment with only 1 of the following ARPIs: enzalutamide, apalutamide or darolutamide. Participants in both Groups D and E must have documented evidence of progression with one or more of the following: * Evidence of radiographic progression of disease following the most recent prostate cancer treatment, defined as progressive disease on CT/MRI per RECIST v1.1 or on a bone scan per PCWG3. Disease spread that is limited to the regional pelvic lymph nodes does not qualify as radiographic progression. * PSA progression defined as the following: * PSA nadir is defined as the lowest PSA during or after the most recent treatment. PSA progression is defined as an increased PSA of at least 25% and ≥1 ng/mL above the nadir confirmed by at least 2 measurements with a minimum of 1 week apart, and with at least 1 of the measurements within 90 days prior to screening. * Participants with mCRPC must have undergone bilateral orchiectomy or received concurrent GnRH agonist or antagonist therapy for at least 6 weeks prior to the first dose of study drug. * Participants with mCSPC or nmCSPC with biochemical recurrence should have received \<6 months of ADT with a GnRH agonist or antagonist or have a history of bilateral orchiectomy (i.e., surgical or medical castration) within 6 months prior to Day 1. Castration therapy (i.e., medical or surgical) must have been started at least 14 days prior to Cycle 1 Day 1 and participants should have no radiographic evidence of disease progression or rising PSA levels after starting ADT and prior to Cycle 1 Day 1. * A serum testosterone level \<50 ng/dL at screening (for mCRPC participants only) * Adequate muscle mass for an i.m. injection * An ECOG PS of 0 or 1 * Adequate bone marrow reserve defined as: * Absolute neutrophil count (ANC) ≥1500/µL * Platelet count ≥100,000/µL * Hemoglobin ≥9 gm/dL * Adequate renal function defined as a serum creatinine ≤1.5 × upper limit of normal (ULN) for the reference laboratory or a calculated creatinine clearance ≥50 mL/min as determined by a validated algorithm for calculating creatinine clearance * Adequate hepatic function, defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN and total bilirubin ≤1.5 × ULN. Exception for elevated bilirubin secondary to Gilbert's disease. Confirmation of Gilbert's diagnosis requires: elevated unconjugated (indirect) bilirubin values; normal complete blood count in previous 12 months, blood smear, and reticulocyte count; normal aminotransferases and alkaline phosphatase in previous 12 months. * Serum albumin ≥3 gm/dL and serum potassium ≥3.5 mEq/L * Participants who are non-sterile and who are heterosexually active with a female partner of childbearing potential must be willing to use a highly effective means of contraception, such as a male condom plus spermicide, from the time of screening, throughout the total duration of the drug treatment, and until 12 weeks after the final dose of PRL-02 or enzalutamide (Group H). * Participant is able to comply with study requirements throughout the study. The Following Inclusion Criteria Apply to Dose Escalation Group H Only * Participants must have one of the following documented conditions: * mCSPC (must have documentation of a positive PMSA-PET or positive bone scan \[for bone disease\] or metastatic lesions on CT or MRI scan \[for soft tissue\]) * mCRPC (must have documentation of a positive PMSA-PET or positive bone scan \[for bone disease\] or metastatic lesions on CT or MRI scan \[for soft tissue\]) * NOTE: For participants in the Dose Escalation Cohorts (including backfill) at ea