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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

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

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03016312
Acronym
IMbassador250
Enrollment
759
Registered
2017-01-10
Start date
2017-01-10
Completion date
2022-12-20
Last updated
2024-08-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

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.

Interventions

DRUGAtezolizumab

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

DRUGEnzalutamide

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

Sponsors

Hoffmann-La Roche
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Overall Survival (OS)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

MeasureTime frameDescription
Time to First Symptomatic Skeletal Event (SSE)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.
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 CriteriaBaseline 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
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 CriteriaMonths 6, 12rPFS 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
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From BaselineBaseline 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
Time to PSA Progression, Assessed as Per PCWG3 CriteriaBaseline 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.
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 CriteriaBaseline 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
Percentage of Participants Who Survived at Month 6 and 12Months 6, 12OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 6 and 12 months
Minimum Observed Serum Concentration (Cmin) of AtezolizumabPre-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.
Maximum Observed Serum Concentration (Cmax) of AtezolizumabDay 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.
Plasma Concentration of EnzalutamidePredose (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 8Safety 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.
Plasma Concentration of N-Desmethyl EnzalutamidePredose (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 8Safety 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.
Number of Participants With Anti-Drug Antibodies (ADAs) to AtezolizumabPredose (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 monthsThe 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.
Percentage of Participants With Adverse EventsBaseline 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.

Countries

Australia, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Poland, Russia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States

Participant flow

Recruitment details

Study was conducted at 155 centres in 21 countries.

Pre-assignment details

Total 759 participants were randomized.

Participants by arm

ArmCount
Atezolizumab + Enzalutamide
Participants received atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity.
379
Enzalutamide
Participants received enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity.
380
Total759

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyDeath210184
Overall Studydiscontinued before the treatment started01
Overall Studyloss to contact10
Overall StudyLost to Follow-up1212
Overall StudyPhysician Decision13
Overall Studystarted a new cancer therapy10
Overall StudyTerminated by the Sponsor's decision100126
Overall StudyWithdrawal by Subject3744

Baseline characteristics

CharacteristicAtezolizumab + EnzalutamideEnzalutamideTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
282 Participants290 Participants572 Participants
Age, Categorical
Between 18 and 65 years
97 Participants90 Participants187 Participants
Age, Continuous70.5 Years
STANDARD_DEVIATION 8.3
70.6 Years
STANDARD_DEVIATION 8.5
70.5 Years
STANDARD_DEVIATION 8.4
Ethnicity (NIH/OMB)
Hispanic or Latino
18 Participants11 Participants29 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
337 Participants345 Participants682 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
24 Participants24 Participants48 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Asian
71 Participants65 Participants136 Participants
Race (NIH/OMB)
Black or African American
7 Participants7 Participants14 Participants
Race (NIH/OMB)
More than one race
2 Participants0 Participants2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants0 Participants1 Participants
Race (NIH/OMB)
Unknown or Not Reported
19 Participants20 Participants39 Participants
Race (NIH/OMB)
White
279 Participants287 Participants566 Participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants
Sex: Female, Male
Male
379 Participants380 Participants759 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
219 / 379191 / 380
other
Total, other adverse events
339 / 374309 / 376
serious
Total, serious adverse events
139 / 37487 / 376

Outcome results

Primary

Overall Survival (OS)

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

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

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureValue (MEDIAN)
Atezolizumab + EnzalutamideOverall Survival (OS)15.2 Months
EnzalutamideOverall Survival (OS)16.6 Months
Comparison: Unstratified Analysisp-value: 0.09495% CI: [0.971, 1.445]Log Rank
Comparison: Stratified Analysisp-value: 0.278695% CI: [0.913, 1.37]Log Rank
Secondary

Maximum Observed Serum Concentration (Cmax) of Atezolizumab

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.

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

Population: PK evaluable population. This population is defined as all randomized participants regardless of whether the assigned study treatment was received. For PK analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Atezolizumab + EnzalutamideMaximum Observed Serum Concentration (Cmax) of Atezolizumab365 Microgram/mLGeometric Coefficient of Variation 26.5
Secondary

Minimum Observed Serum Concentration (Cmin) of Atezolizumab

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.

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)

Population: PK evaluable population. This population is defined as all randomized participants regardless of whether the assigned study treatment was received. For PK analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabUnscheduled Predose32.9 microgram/mLGeometric Coefficient of Variation 326.5
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 2, Day 1, pre-dose76.4 microgram/mLGeometric Coefficient of Variation 69.4
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 3, Day 1, pre-dose124 microgram/mLGeometric Coefficient of Variation 79.5
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 4, Day 1, pre-dose147 microgram/mLGeometric Coefficient of Variation 65.1
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 8, Day 1, pre-dose157 microgram/mLGeometric Coefficient of Variation 305.9
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 12, Day 1, pre-dose155 microgram/mLGeometric Coefficient of Variation 497.4
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 16, Day 1, pre-dose137 microgram/mLGeometric Coefficient of Variation 144.9
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabSafety visit2.69 microgram/mLGeometric Coefficient of Variation 1759.3
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabStudy Completion/Early Discontinuation82.3 microgram/mLGeometric Coefficient of Variation 1008.1
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabStudy Completion/Early Discontinuation pre-dose65.3 microgram/mLGeometric Coefficient of Variation 106.9
Atezolizumab + EnzalutamideMinimum Observed Serum Concentration (Cmin) of AtezolizumabUnscheduled50.5 microgram/mL
UnknownMinimum Observed Serum Concentration (Cmin) of AtezolizumabCycle 1, Day 1, pre-dose microgram/mL
Secondary

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

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.

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

Population: The safety population is defined as participants who received any amount of any component of the study treatments (atezolizumab, or enzalutamide). Participants will be allocated to treatment arms according to the treatment they actually received (i.e., participants randomized to enzalutamide alone who received at least one full or partial dose of atezolizumab will be included in the atezolizumab arm for safety).

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Atezolizumab + EnzalutamideNumber of Participants With Anti-Drug Antibodies (ADAs) to AtezolizumabWith Positive Sample at Baseline2 Participants
Atezolizumab + EnzalutamideNumber of Participants With Anti-Drug Antibodies (ADAs) to AtezolizumabWithout Positive Sample at Baseline368 Participants
Atezolizumab + EnzalutamideNumber of Participants With Anti-Drug Antibodies (ADAs) to AtezolizumabParticipants positive for Treatment Emergent ADA: treatment induced52 Participants
Atezolizumab + EnzalutamideNumber of Participants With Anti-Drug Antibodies (ADAs) to AtezolizumabParticipants positive for Treatment Emergent ADA: treatment enhanced0 Participants
Atezolizumab + EnzalutamideNumber of Participants With Anti-Drug Antibodies (ADAs) to AtezolizumabParticipants negative for Treatment Emergent ADA320 Participants
Secondary

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

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

Time frame: Months 6, 12

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureGroupValue (NUMBER)
Atezolizumab + EnzalutamidePercentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria6 months41.84 Percentage of Participants
Atezolizumab + EnzalutamidePercentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria12 months14.89 Percentage of Participants
EnzalutamidePercentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria6 months39.64 Percentage of Participants
EnzalutamidePercentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria12 months13.45 Percentage of Participants
Comparison: Difference in Event Free Rate - 6 monthsp-value: 0.595995% CI: [-5.95, 10.37]z-test
Comparison: Difference in Event Free Rate - 12 monthsp-value: 0.626295% CI: [-4.35, 7.23]z-test
Secondary

Percentage of Participants Who Survived at Month 6 and 12

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

Time frame: Months 6, 12

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureGroupValue (NUMBER)
Atezolizumab + EnzalutamidePercentage of Participants Who Survived at Month 6 and 126 Months85.12 Percentage of Participants
Atezolizumab + EnzalutamidePercentage of Participants Who Survived at Month 6 and 1212 Months60.61 Percentage of Participants
EnzalutamidePercentage of Participants Who Survived at Month 6 and 126 Months85.32 Percentage of Participants
EnzalutamidePercentage of Participants Who Survived at Month 6 and 1212 Months64.65 Percentage of Participants
Comparison: Difference in Event Free Rate - 6 monthsp-value: 0.939195% CI: [-5.38, 4.97]z-test
Comparison: Difference in Event Free Rate - 12 monthsp-value: 0.270695% CI: [-11.21, 3.14]z-test
Secondary

Percentage of Participants With Adverse Events

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

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

Population: The safety population is defined as participants who received any amount of any component of the study treatments (atezolizumab, or enzalutamide). Participants will be allocated to treatment arms according to the treatment they actually received (i.e., participants randomized to enzalutamide alone who received at least one full or partial dose of atezolizumab will be included in the atezolizumab arm for safety)

ArmMeasureGroupValue (NUMBER)
Atezolizumab + EnzalutamidePercentage of Participants With Adverse EventsTotal number of participants with at least one adverse event96.8 Percentage of Participants
Atezolizumab + EnzalutamidePercentage of Participants With Adverse EventsTotal number of participants with at least one treatment related AE78.1 Percentage of Participants
EnzalutamidePercentage of Participants With Adverse EventsTotal number of participants with at least one adverse event92.3 Percentage of Participants
EnzalutamidePercentage of Participants With Adverse EventsTotal number of participants with at least one treatment related AE51.6 Percentage of Participants
Secondary

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

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

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

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureValue (NUMBER)
Atezolizumab + EnzalutamidePercentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline25.9 Percentage of Participants
EnzalutamidePercentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline24.2 Percentage of Participants
2% CI: [-4.5, 7.8]
Secondary

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

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

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

Population: * Participants were classified as missing or unevaluable if no post-baseline response assessments were available or all post-baseline response baseline assessments were unevaluable.~* Responders had to have a CR or PR on two consecutive occasions at least 6 weeks apart.

ArmMeasureValue (NUMBER)
Atezolizumab + EnzalutamidePercentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria13.7 Percentage of Participants
EnzalutamidePercentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria7.4 Percentage of Participants
Secondary

Plasma Concentration of Enzalutamide

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.

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

Population: PK evaluable population

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
Atezolizumab + EnzalutamidePlasma Concentration of EnzalutamideCycle 1 Day 1 1 Hr Post1.51 Microgram/mLGeometric Coefficient of Variation 406.4
Atezolizumab + EnzalutamidePlasma Concentration of EnzalutamideCycle 3 Day 1 1 Hr Post14.2 Microgram/mLGeometric Coefficient of Variation 27.3
Atezolizumab + EnzalutamidePlasma Concentration of EnzalutamideCycle 8 Day 1 Predose11.3 Microgram/mLGeometric Coefficient of Variation 103.7
Atezolizumab + EnzalutamidePlasma Concentration of EnzalutamideCycle 3 Day 1 Predose13.1 Microgram/mLGeometric Coefficient of Variation 29
EnzalutamidePlasma Concentration of EnzalutamideCycle 8 Day 1 Predose12.6 Microgram/mLGeometric Coefficient of Variation 30.5
EnzalutamidePlasma Concentration of EnzalutamideUnscheduled Predose10.5 Microgram/mL
EnzalutamidePlasma Concentration of EnzalutamideCycle 1 Day 1 1 Hr Post2.42 Microgram/mLGeometric Coefficient of Variation 270.6
EnzalutamidePlasma Concentration of EnzalutamideCycle 3 Day 1 Predose13.8 Microgram/mLGeometric Coefficient of Variation 20.7
EnzalutamidePlasma Concentration of EnzalutamideCycle 3 Day 1 1 Hr Post16.0 Microgram/mLGeometric Coefficient of Variation 19.8
UnknownPlasma Concentration of EnzalutamideCycle 1 Day 1 Predose Microgram/mL
Secondary

Plasma Concentration of N-Desmethyl Enzalutamide

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.

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

Population: PK evaluable population

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
Atezolizumab + EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 3 Day 1 1 Hr Post10.6 Microgram/mLGeometric Coefficient of Variation 34.2
Atezolizumab + EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 3 Day 1 Predose11.9 Microgram/mLGeometric Coefficient of Variation 33.1
Atezolizumab + EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 8 Day 1 Predose12.8 Microgram/mLGeometric Coefficient of Variation 36.8
Atezolizumab + EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 1 Day 1 1 Hr Post0.02 Microgram/mL
EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 8 Day 1 Predose13.1 Microgram/mLGeometric Coefficient of Variation 32.6
EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideUnscheduled Predose13.3 Microgram/mL
EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 1 Day 1 1 Hr Post0.03 Microgram/mL
EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 3 Day 1 Predose11.9 Microgram/mLGeometric Coefficient of Variation 28.8
EnzalutamidePlasma Concentration of N-Desmethyl EnzalutamideCycle 3 Day 1 1 Hr Post10.9 Microgram/mLGeometric Coefficient of Variation 29.8
UnknownPlasma Concentration of N-Desmethyl EnzalutamideCycle 1 Day 1 Predose Microgram/mL
Secondary

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

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

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

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureValue (MEDIAN)
Atezolizumab + EnzalutamideRadiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria4.2 Months
EnzalutamideRadiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria4.1 Months
Comparison: Unstratified Analysisp-value: 0.315795% CI: [0.775, 1.086]Log Rank
Comparison: Stratified Analysisp-value: 0.236695% CI: [0.754, 1.072]Log Rank
Secondary

Time to First Symptomatic Skeletal Event (SSE)

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.

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

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants from whom data was collected and analyzed.

ArmMeasureValue (MEDIAN)
Atezolizumab + EnzalutamideTime to First Symptomatic Skeletal Event (SSE)24.1 Months
EnzalutamideTime to First Symptomatic Skeletal Event (SSE)24.9 Months
Secondary

Time to PSA Progression, Assessed as Per PCWG3 Criteria

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.

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

Population: The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, Number Analyzed refers to number of participants in the ITT population with measurable soft tissue lesions at baseline.

ArmMeasureValue (MEDIAN)
Atezolizumab + EnzalutamideTime to PSA Progression, Assessed as Per PCWG3 Criteria2.8 Months
EnzalutamideTime to PSA Progression, Assessed as Per PCWG3 Criteria2.8 Months
Comparison: Unstratified Analysisp-value: 0.535995% CI: [0.89, 1.251]Log Rank
Comparison: Stratified Analysisp-value: 0.685795% CI: [0.869, 1.238]Log Rank

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026