A Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide in Participants With Metastatic Castration-Resistant Prostrate Cancer (mCRPC) After Failure of an Androgen Synthesis Inhibitor And Failure of, Ineligibility For, or Refusal of a Taxane Regimen (IMbassador250)

Roche

Status and phase: Completed; Phase 3

Conditions: Prostatic Neoplasms, Castration-Resistant

Treatments: Drug: Atezolizumab; Drug: Enzalutamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03016312

2016-003092-22 (EudraCT Number)

CO39385

Details and patient eligibility

About

This Phase III, multicenter, randomized, open-label study will evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] antibody) in combination with enzalutamide compared with enzalutamide alone in participants with mCRPC after failure of an androgen synthesis inhibitor (e.g., abiraterone) and failure of, ineligibility for, or refusal of a taxane regimen. Participants will be randomized to one of the two treatment arms (atezolizumab in combination with enzalutamide, and enzalutamide alone) in a 1:1 ratio (experimental to control arm) in global randomized phase. Participants will receive treatment until investigator-assessed confirmed radiographic disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria or unacceptable toxicity.

Enrollment: 759 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (>/=) 3 months
• Histologically confirmed adenocarcinoma of the prostate
• Known castrate-resistant disease with serum testosterone level less than or equal to (</=) 50 nanograms per deciliter (ng/dL) with prior surgical castration or ongoing androgen deprivation for the duration of the study
• Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration
• One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen
• Progression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancer
• Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death-ligand 1 (PD-L1) status via central testing
• Adequate hematologic and end organ function

Exclusion criteria

• Prior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor (e.g., apalutamide, ODM-201)
• Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment
• Treatment with abiraterone within 2 weeks prior to study treatment
• Structurally unstable bone lesions suggesting impending fracture
• Known or suspected brain metastasis or active leptomeningeal disease
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
• Active or history of autoimmune disease or immune deficiency
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Positive human immunodeficiency virus (HIV) test, active tuberculosis, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
• History of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attack

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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759 participants in 2 patient groups

Atezolizumab + Enzalutamide

Experimental group

Description:

Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).

Treatment:

Drug: Enzalutamide

Drug: Atezolizumab

Enzalutamide

Active Comparator group

Description:

Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).

Treatment:

Drug: Enzalutamide