Safety and Tolerability of Atezolizumab (ATZ) in Combination With Radium-223 Dichloride (R-223-D) in Metastatic Castrate-Resistant Prostate Cancer (CRPC) Progressed Following Treatment With an Androgen Pathway Inhibitor

This study is designed to assess the safety and tolerability of atezolizumab when given in combination with radium-223 dichloride in participants with metastatic CRPC who have progressed after treatment with an androgen pathway inhibitor. This adaptive design study includes a cohort phase and a potential randomization phase. An initial concurrent dosing evaluation will evaluate the safety and tolerability of a treatment regimen that employs a concurrent start time for atezolizumab and radium-223 dichloride (Cohort 1). If concurrent dosing is found to be safe and tolerable in Cohort 1, additional participants will be enrolled and eligible participants will be randomized in a 1:1:1 ratio to Arms A, B, and C. If concurrent dosing is not tolerated in Cohort 1, new participants will be enrolled in a staggered dosing evaluation: Cohort 2 (28-day radium-223 dichloride run-in, atezolizumab will begin on Day 1 of Cycle 2) and Cohort 3 (56-day radium-223 dichloride run-in, atezolizumab will begin on Day 1 of Cycle 3). If the Cohort 2 schedule is tolerable, then additional participants will be enrolled using this treatment schedule; If the Cohort 2 schedule is not tolerable, subsequent participants will be enrolled in Cohort 3. If the Cohort 3 schedule is tolerable, then additional participants will be enrolled using this treatment schedule. If Cohort 3 schedule is not tolerable, no additional participant will be enrolled in the study.


Eligibility Criteria:
Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy greater than or equal to (\>/=) 12 weeks
* Histologically confirmed, castrate-resistant adenocarcinoma of the prostate
* Measurable disease according to RECIST v1.1
* Multiple bone metastases within 12 weeks prior to study drug
* Participants receiving bisphosphonate or denosumab therapy must have been on a stable dose for at least 4 weeks
* Visceral metastasis and/or lymphadenopathy
* Tumors that are amenable to serial biopsy
* Disease progression according to Prostate Cancer Working Group 2 (PCWG2) criteria during or following treatment with at least one second generation androgen pathway inhibitor (for example, enzalutamide, abiraterone) for metastatic prostate cancer
* Adequate hematologic and end-organ function
* One prior taxane-containing regimen for mCRPC, or refusal or ineligibility of a taxane-containing regimen

Exclusion Criteria:

* History of small-cell or neuroendocrine prostate carcinoma
* Treatment with approved anti-cancer therapy (with the exception of abiraterone) within 3 weeks of study drug. Abiraterone must not be administered within 2 weeks prior to initiation of study treatment
* Participation in another clinical trial/investigation within 28 days prior to study drug
* Brain metastases or active leptomeningeal disease (with the exception of participants with treated epidural disease and no other epidural progression)
* Uncontrolled tumor-related pain
* Uncontrolled hypercalcemia
* Significant cardiovascular disease
* History of autoimmune disease except controlled/treated hypothyroidism, type 1 diabetes mellitus, or certain skin disorders
* Prior allogeneic stem cell or solid organ transplant
* History of pulmonary fibrosis/inflammation, including active tuberculosis
* Human immunodeficiency virus (HIV) or hepatitis B or C
* Prior treatment with cluster of differentiation (CD) 137 agonist, anti-programmed death (PD) 1, or anti-programmed death ligand (PD-L) 1 therapeutic antibody or pathway-targeting agents
* Immunostimulants within 4 weeks or immunosuppressants within 14 days prior to study drug
* Prior radium-223 dichloride or hemibody external radiotherapy
* Systemic strontium-89, samarium-153, rhenium-186, or rhenium-188 for bone metastases within 24 weeks prior to initiation of study treatment
* Spinal compression or structurally unstable bone lesions suggesting impending pathologic fractures based on clinical findings and/or magnetic resonance imaging (MRI)
* Bone marrow dysplasia
* Unmanageable fecal incontinence