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Phase 3 N=759 Randomized Treatment

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

Prostatic Neoplasms, Castration-Resistant

Enrolled (actual)
759
Serious AEs
30.1%
Results posted
Apr 2021
Primary outcome: Primary: Overall Survival (OS) — 15.2; 16.6 Months — p=0.0940

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Atezolizumab (Drug); Enzalutamide (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
Male
Sponsor
Hoffmann-La Roche
Primary completion
Jun 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Overall Survival (OS)
15.2; 16.6 0.0940
SECONDARY
Percentage of Participants Who Survived at Month 6 and 12
85.12; 85.32; 60.61; 64.65 0.9391
SECONDARY
Time to First Symptomatic Skeletal Event (SSE)
24.1; 24.9
SECONDARY
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria
4.2; 4.1 0.3157
SECONDARY
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria
41.84; 39.64; 14.89; 13.45 0.5959
SECONDARY
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline
25.9; 24.2
SECONDARY
Time to PSA Progression, Assessed as Per PCWG3 Criteria
2.8; 2.8 0.5359
SECONDARY
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria
13.7; 7.4
SECONDARY
Percentage of Participants With Adverse Events
96.8; 92.3; 78.1; 51.6
SECONDARY
Minimum Observed Serum Concentration (Cmin) of Atezolizumab
76.4; 124; 147; 157; 155; 137
SECONDARY
Maximum Observed Serum Concentration (Cmax) of Atezolizumab
365
SECONDARY
Plasma Concentration of Enzalutamide
1.51; 2.42; 13.1; 13.8; 14.2; 16.0
SECONDARY
Plasma Concentration of N-Desmethyl Enzalutamide
0.02; 0.03; 11.9; 11.9; 10.6; 10.9
SECONDARY
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
2; 368; 52; 0; 320

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.

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
  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03016312). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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