• Patients must meet the following criteria in order to be included in both the Phase 1 and Phase 2a parts of the trial:

• Male and ≥ 18 years

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis

• Disease progression on any one of the following: prior enzalutamide, abiraterone, apalutamide or related agent therapy as defined by meeting at least one of the following criteria per the investigator in accordance with the Prostate Cancer Working Group 3 (PCWG3) criteria \[Scher et al, 2016\]:

∙ PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart, ideally three successive measurements

‣ Soft tissue disease progression defined as \>20% increase in sum of diameters of all target lesions based on sum of diameters since treatment started or the appearance of 1 or more new lesions by RECIST 1.1

‣ Bone disease progression defined by two or more new lesions on bone scan

• Serum testosterone level \< 50 ng/dL (\< 0.5 ng/mL, \< 1.7 nmol/L). Patients may have ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) super-agonist or antagonist, and/or be surgically or medically castrated.

• Patients must have PSMA positive lesions. These are defined as having Ga 68-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. PSMA-negative lesions are defined as having PSMA uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any metastatic solid-organ lesions with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of at least 1.0 cm in the short axis.

• Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Day 1

• Patients who have received a taxane or are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy include the following:

∙ Poor performance status

‣ Prior intolerance to cytotoxic agents

‣ Other serious medical conditions such as symptomatic peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator

• ECOG PS of 0 to 2 for Phase 1 and 0 to 1 for Phase 2a

• Estimated life expectancy of at least 3 months for Phase 1 and 6 months for Phase 2a as determined by the Investigator.

⁃ For patients who have partners of childbearing potential, the partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration.

⁃ Able and willing to provide signed informed consent and comply with protocol requirements