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

Status:	Active, not recruiting
Conditions:	Prostate Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	3/7/2019
Start Date:	September 23, 2016
End Date:	March 31, 2020

A Phase Ib, Open-Label Study of the Safety and Tolerability of Atezolizumab in Combination With Radium-223 Dichloride in Patients With Castrate-Resistant Prostate Cancer Who Have 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.

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

We found this trial at

sites

Memorial Sloan-Kettering Cancer Center

Commack, New York 11725

from

Commack, NY