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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03016312




Registration number
NCT03016312
Ethics application status
Date submitted
9/01/2017
Date registered
10/01/2017
Date last updated
10/06/2021

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2016-003092-22
Secondary ID [2] 0 0
CO39385
Universal Trial Number (UTN)
Trial acronym
IMbassador250
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms, Castration-Resistant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Enzalutamide

Experimental: 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).

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


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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - Overall Survival is defined as the time from randomization to death from any cause.
Timepoint [1] 0 0
Baseline until death from any cause (up to approximately 42 months)
Secondary outcome [1] 0 0
Percentage of Participants Who Survived at Month 12 and 24 - OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 12 and 24 months
Timepoint [1] 0 0
Months 12, 24
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline up to end of study (up to approximately 42 months)
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline until disease progression or death from any cause (up to approximately 42 months)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Months 6, 12
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline until disease progression (up to approximately 42 months)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline until disease progression (up to approximately 42 months)
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline until disease progression or death from any cause (up to approximately 42 months)
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline up to end of study (up to approximately 42 month
Secondary outcome [9] 0 0
Minimum Observed Serum Concentration (Cmin) of Atezolizumab - Atezolizumab serum concentration data (minimum [Cmin]) will be reported and summarized for each cycle where collected as appropriate.
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Maximum Observed Serum Concentration (Cmax) of Atezolizumab - Atezolizumab serum concentration data (maximum [Cmax]) will be reported and summarized for each cycle where collected as appropriate.
Timepoint [10] 0 0
Pre-infusion (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5 hr post-infusion (infusion duration: 60 minutes [min]) on Day 1 Cycle 1; treatment discontinuation visit, 120 days after last dose (up to approximately 42 months)
Secondary outcome [11] 0 0
Plasma Concentration of Enzalutamide - Plasma concentrations of Enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Plasma Concentration of N-Desmethyl Enzalutamide - Plasma concentrations of N-desmethyl enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab - The numbers and proportions of ATA-positive participants and ATA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group.
Timepoint [13] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Eastern Health; Cancer Services - Box Hill
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital; Concord Cancer Centre - Concord
Recruitment hospital [3] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [4] 0 0
Royal Brisbane & Women's Hosp; Cancer Care Serv - Herston
Recruitment hospital [5] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [6] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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Colorado
Country [3] 0 0
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Connecticut
Country [4] 0 0
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Florida
Country [5] 0 0
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Indiana
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Massachusetts
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Michigan
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Nebraska
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Nevada
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Lódz
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Leningrad
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Moscow
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Barcelona
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Malaga
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Bern
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Leicester
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Manchester
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03016312
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications