Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC

Inclusion Criteria:

* Men with histologically or cytologically confirmed adenocarcinoma of the prostate
* Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or mCSPC, M0 CRPC, or mCRPC
* Surgical or medical castration, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening
* Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment defined by at least one of the following: measurable visceral disease (eg, adrenal, kidney, liver, lung, pancreas, spleen) per RECIST 1.1; OR measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation)
* Progressive disease at study entry as defined by specific criteria for prostate specific antigen (PSA) progression OR soft tissue disease progression in the opinion of the Investigator (Note: subjects with bone disease progression alone are not eligible)
* Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the day of consent
* ECOG performance status of 0 or 1
* Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator
* Adequate organ and marrow function based upon specific laboratory assessments obtained within 21 days prior to randomization
* Understanding and ability to comply with protocol requirements

Exclusion Criteria:

* Any prior nonhormonal therapy initiated for the treatment of mCRPC
* Receipt of abiraterone within 1 week; cyproterone within 10 days; or flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2 weeks before randomization
* Radiation therapy within 4 weeks (2 weeks for bone metastases) prior to randomization (subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible)
* Known brain metastases or cranial epidural disease unless adequately treated and clinically stable at least 4 weeks prior to randomization
* Symptomatic or impending spinal cord compression or cauda equina syndrome
* Concomitant anticoagulation with oral anticoagulants (some specific exceptions apply)
* Administration of a live, attenuated vaccine within 30 days prior to randomization
* Systematic treatment with, or any condition requiring, either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization
* Uncontrolled, significant intercurrent or recent illness
* Major surgery within 4 weeks prior to randomization
* Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms per ECG within 21 days before randomization
* Inability or unwillingness to swallow pills or receive IV administration
* Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies
* Any other active malignancy at time of randomization or diagnosis of another malignancy within 2 years prior to randomization that requires active treatment (some exceptions apply such as locally curable cancers that have apparently been cured).