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

Conditions: Castrate-Resistant Prostate Cancer

Summary: 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