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Completed

NCT Number: NCT03016312

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

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.

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Key information

Conditions

Prostatic Neoplasms, Castration-Resistant Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Eastern Health; Cancer Services, Box Hill, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Atezolizumab

Drug

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.

Other names: Tecentriq®

Enzalutamide

Drug

Enzalutamide capsules will be administered orally at a dose of 160 mg daily.

Other names: Xtandi®

Primary outcomes

  1. 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

  1. Percentage of Participants Who Survived at Month 6 and 12

    Time frame: Months 6, 12

    OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 6 and 12 months

  2. Time to First Symptomatic Skeletal Event (SSE)

    Time frame: Baseline up to end of study (up to approximately 42 months)

    An SSE is defined as external beam radiation therapy to relieve skeletal symptoms (including initiation of radium-223 dichloride or other types of radionuclide therapy to treat symptoms of bone metastases), new symptomatic pathologic bone fracture, clinically apparent occurrence of spinal cord compression, or tumor related orthopedic surgical intervention.

  3. Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria

    Time frame: Baseline until disease progression or death from any cause (up to approximately 42 months)

    rPFS is defined as the time from randomization to the earliest occurrence of one of the following:

    • A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented.
    • Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1
    • Death from any cause

  4. Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria

    Time frame: Months 6, 12

    rPFS is defined as the time from randomization to the earliest occurrence of one of the following:

    • A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented.
    • Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1
    • Death from any cause

  5. Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline

    Time frame: Baseline until disease progression (up to approximately 42 months)

    PSA response rate, defined as a > 50% decrease in PSA from baseline that is confirmed after ≥ 3 weeks by a consecutive confirmatory PSA measurement

  6. Time to PSA Progression, Assessed as Per PCWG3 Criteria

    Time frame: Baseline until disease progression (up to approximately 42 months)

    In participants with no PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the baseline value, ≥12 weeks after baseline. In participants with an initial PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥3 weeks later.

  7. Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria

    Time frame: Baseline until disease progression or death from any cause (up to approximately 42 months)

    Objective response rate in soft tissue lesions, defined as the percentage of participants with either a CR or PR on two consecutive occasions ≥ 6 weeks apart, as determined by the investigator through use of PCWG3 criteria

  8. Percentage of Participants With Adverse Events

    Time frame: Baseline up to end of study (up to approximately 42 month)

    Verbatim description of adverse events will be coded to MedDRA preferred terms and graded according to NCI CTCAE v4.0.

  9. Minimum Observed Serum Concentration (Cmin) of Atezolizumab

    Time frame: 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)

    Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.

  10. Maximum Observed Serum Concentration (Cmax) of Atezolizumab

    Time frame: Day Cycle 1 Day 1 0.5 hr post-infusion (infusion duration: 60 minutes [min])

    Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.

  11. Plasma Concentration of Enzalutamide

    Time frame: 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

    Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.

  12. Plasma Concentration of N-Desmethyl Enzalutamide

    Time frame: 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

    Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.

  13. Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

    Time frame: 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

    The numbers and proportions of ADA-positive participants and ADA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group.

    Enzalutamide Arm has no Atezolizumab dosing therefore no participants to include here for Atezolizumab ADA.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

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

Acronym: IMbassador250

Important dates

Study start
2017
Primary completion
2019
Study completion
2022
First posted
Jan 10, 2017
Registry last updated
Aug 9, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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