NCT03016312: IMbassador250

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

Completed Phase 3 Results posted Last updated 9 August 2024

What this trial tests

Phase 3 trial testing Atezolizumab in Prostatic Neoplasms, Castration-Resistant in 759 participants. Completed in 20 December 2022.

Timeline

10 January 2017

Primary endpoint
24 June 2019

20 December 2022

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	759
Start date	10 January 2017
Primary completion	24 June 2019
Estimated completion	20 December 2022
Sites	158 locations across Italy, Japan, Taiwan, Poland, South Korea, Denmark, Russia, Belgium

Drugs / interventions tested

• Atezolizumab (atezolizumab) — full drug profile →
• Enzalutamide (enzalutamide) — full drug profile →

Conditions studied

• Prostatic Neoplasms, Castration-Resistant — all drugs for Prostatic Neoplasms, Castration-Resistant →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, male only, with Prostatic Neoplasms, Castration-Resistant. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Primary · 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.

Group	Value	95% CI
Atezolizumab + Enzalutamide	15.2	14.0 – 17.0
Enzalutamide	16.6	14.7 – 18.4

Percentage of Participants Who Survived at Month 6 and 12 Secondary · Months 6, 12

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

6 Months

Group	Value	95% CI
Atezolizumab + Enzalutamide	85.12	81.45 – 88.78
Enzalutamide	85.32	81.67 – 88.97

12 Months

Group	Value	95% CI
Atezolizumab + Enzalutamide	60.61	55.52 – 65.71
Enzalutamide	64.65	59.60 – 69.70

Time to First Symptomatic Skeletal Event (SSE) Secondary · 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.

Group	Value	95% CI
Atezolizumab + Enzalutamide	24.1	24.1 – NA
Enzalutamide	24.9	24.9 – NA

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

Group	Value	95% CI
Atezolizumab + Enzalutamide	4.2	4.1 – 5.3
Enzalutamide	4.1	3.7 – 4.5

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

6 months

Group	Value	95% CI
Atezolizumab + Enzalutamide	41.84	36.09 – 47.60
Enzalutamide	39.64	33.86 – 45.42

12 months

Group	Value	95% CI
Atezolizumab + Enzalutamide	14.89	10.74 – 19.05
Enzalutamide	13.45	9.42 – 17.49

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

Group	Value	95% CI
Atezolizumab + Enzalutamide	25.9	21.5 – 30.5
Enzalutamide	24.2	20.0 – 28.7

Time to PSA Progression, Assessed as Per PCWG3 Criteria Secondary · 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.

Group	Value	95% CI
Atezolizumab + Enzalutamide	2.8	2.8 – 2.9
Enzalutamide	2.8	2.8 – 2.9

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

Group	Value	95% CI
Atezolizumab + Enzalutamide	13.7	8.4 – 20.7
Enzalutamide	7.4	3.7 – 13.0

Percentage of Participants With Adverse Events Secondary · 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.

Total number of participants with at least one adverse event

Group	Value	95% CI
Atezolizumab + Enzalutamide	96.8
Enzalutamide	92.3

Total number of participants with at least one treatment related AE

Group	Value	95% CI
Atezolizumab + Enzalutamide	78.1
Enzalutamide	51.6

Minimum Observed Serum Concentration (Cmin) of Atezolizumab Secondary · 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-Participan

Cycle 2, Day 1, pre-dose

Group	Value	95% CI
Atezolizumab + Enzalutamide	76.4	± 69.4

Cycle 3, Day 1, pre-dose

Group	Value	95% CI
Atezolizumab + Enzalutamide	124	± 79.5

Cycle 4, Day 1, pre-dose

Group	Value	95% CI
Atezolizumab + Enzalutamide	147	± 65.1

Cycle 8, Day 1, pre-dose

Group	Value	95% CI
Atezolizumab + Enzalutamide	157	± 305.9

Cycle 12, Day 1, pre-dose

Group	Value	95% CI
Atezolizumab + Enzalutamide	155	± 497.4

Cycle 16, Day 1, pre-dose

Group	Value	95% CI
Atezolizumab + Enzalutamide	137	± 144.9

Safety visit

Group	Value	95% CI
Atezolizumab + Enzalutamide	2.69	± 1759.3

Maximum Observed Serum Concentration (Cmax) of Atezolizumab Secondary · 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-Participan

Group	Value	95% CI
Atezolizumab + Enzalutamide	365	± 26.5

Plasma Concentration of Enzalutamide Secondary · 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-Participan

Cycle 1 Day 1 1 Hr Post

Group	Value	95% CI
Atezolizumab + Enzalutamide	1.51	± 406.4
Enzalutamide	2.42	± 270.6

Cycle 3 Day 1 Predose

Group	Value	95% CI
Atezolizumab + Enzalutamide	13.1	± 29.0
Enzalutamide	13.8	± 20.7

Cycle 3 Day 1 1 Hr Post

Group	Value	95% CI
Atezolizumab + Enzalutamide	14.2	± 27.3
Enzalutamide	16.0	± 19.8

Cycle 8 Day 1 Predose

Group	Value	95% CI
Atezolizumab + Enzalutamide	11.3	± 103.7
Enzalutamide	12.6	± 30.5

Unscheduled Predose

Group	Value	95% CI
Enzalutamide	10.5	± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline Up To 4 Years 11 Months. For outcome measures and ADA measurements, the time frame was up to 42 (3 years and 6 months) months. However for Adverse Events, the duration of the timeframe was 4 years 11 month. The study was terminated earlier than the planned date and stopped for the efficacy outcomes. And participants' safety was followed up for longer time period.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Atezolizumab + Enzalutamide

Serious: 139/374 (37%)

Deaths: 219/379

Enzalutamide

Serious: 87/376 (23%)

Deaths: 191/380

Serious adverse events (179 terms)

Reaction	System	Atezolizumab + Enzalutamide	Enzalutamide
Anaemia	Blood and lymphatic system disorders	—	—
Pneumonia	Infections and infestations	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Haematuria	Renal and urinary disorders	—	—
Pyrexia	General disorders	—	—
Asthenia	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Sepsis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Adrenal insufficiency	Endocrine disorders	—	—
Chest pain	General disorders	—	—
Fatigue	General disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—
Platelet count decreased	Investigations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Myositis	Musculoskeletal and connective tissue disorders	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Coronary artery disease	Cardiac disorders	—	—

Other adverse events (31 terms — click to expand)

Reaction	System	Atezolizumab + Enzalutamide	Enzalutamide
Fatigue	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Asthenia	General disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Weight decreased	Investigations	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Oedema peripheral	General disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Headache	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Hypertension	Vascular disorders	—	—
Dizziness	Nervous system disorders	—	—
Pain	General disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Hot flush	Vascular disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Urinary tract infection	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—

Most-reported serious reactions: Anaemia, Pneumonia, Bone pain, Haematuria, Pyrexia, Asthenia, Back pain, Acute kidney injury.

Data from ClinicalTrials.gov NCT03016312 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
   Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
2. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
   Alsaab HO, Sau S, Alzhrani R, Tatiparti K, et al · · 2017 · cited 1206× · PMID 28878676 · DOI 10.3389/fphar.2017.00561
3. Genetics and biology of prostate cancer.
   Wang G, Zhao D, Spring DJ, DePinho RA. · · 2018 · cited 527× · PMID 30181359 · DOI 10.1101/gad.315739.118
4. Treatment of Advanced Prostate Cancer.
   Teo MY, Rathkopf DE, Kantoff P. · · 2019 · cited 516× · PMID 30691365 · DOI 10.1146/annurev-med-051517-011947
5. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
   Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
6. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial.
   Powles T, Yuen KC, Gillessen S, Kadel EE, et al · · 2022 · cited 207× · PMID 35013615 · DOI 10.1038/s41591-021-01600-6
7. How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer.
   Stultz J, Fong L. · · 2021 · cited 173× · PMID 33820953 · DOI 10.1038/s41391-021-00340-5
8. Revisiting Immunotherapy: A Focus on Prostate Cancer.
   Cha HR, Lee JH, Ponnazhagan S. · · 2020 · cited 169× · PMID 32066566 · DOI 10.1158/0008-5472.can-19-2948