A Phase III, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide Versus Enzalutamide Alone in Patients With Metastatic Castration-Resistant Prostate Cancer After Failure of an Androgen Synthesis Inhibitor and Failure of, Ineligibility for, or Refusal of a Taxane Regimen

Hoffmann-La Roche158 sites in 4 countries759 target enrollmentJanuary 10, 2017

ConditionsProstatic Neoplasms, Castration-Resistant

InterventionsAtezolizumab Enzalutamide

DrugsAtezolizumab Enzalutamide

Overview

Phase: Phase 3
Intervention: Atezolizumab
Conditions: Prostatic Neoplasms, Castration-Resistant
Sponsor: Hoffmann-La Roche
Enrollment: 759
Locations: 158
Primary Endpoint: Overall Survival (OS)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

January 10, 2017

End Date

December 20, 2022

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Atezolizumab + Enzalutamide

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).

Intervention: Atezolizumab

Atezolizumab + Enzalutamide

Intervention: Enzalutamide

Enzalutamide

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

Intervention: Enzalutamide

Outcomes

Primary Outcomes

Overall Survival (OS)

Time Frame: Baseline until death from any cause (up to approximately 42 months)

Overall Survival is defined as the time from randomization to death from any cause.

Secondary Outcomes

Time to PSA Progression, Assessed as Per PCWG3 Criteria(Baseline until disease progression (up to approximately 42 months))
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria(Baseline until disease progression or death from any cause (up to approximately 42 months))
Percentage of Participants With Adverse Events(Baseline up to end of study (up to approximately 42 month))
Plasma Concentration of Enzalutamide(Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8)
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria(Baseline until disease progression or death from any cause (up to approximately 42 months))
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria(Months 6, 12)
Minimum Observed Serum Concentration (Cmin) of Atezolizumab(Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months))
Plasma Concentration of N-Desmethyl Enzalutamide(Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8)
Percentage of Participants Who Survived at Month 6 and 12(Months 6, 12)
Time to First Symptomatic Skeletal Event (SSE)(Baseline up to end of study (up to approximately 42 months))
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline(Baseline until disease progression (up to approximately 42 months))
Maximum Observed Serum Concentration (Cmax) of Atezolizumab(Day Cycle 1 Day 1 0.5 hr post-infusion (infusion duration: 60 minutes [min]))
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months)