Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer (AMBASSADOR)
Phase III Randomized Adjuvant Study of Pembrolizumab in muScle invaSive and locAlly aDvanced urOthelial caRcinoma (AMBASSADOR) Versus Observation
Sponsor: National Cancer Institute (NCI)
A observational or N/A phase clinical study on Localized Renal Pelvis and Ureter Urothelial Carcinoma and Locally Advanced Bladder Urothelial Carcinoma, this trial is ongoing. The trial is conducted by National Cancer Institute (NCI) and has accumulated 96 data snapshots since 2017. Oncology trials at this stage typically focus on safety, tolerability, and early efficacy signals.
Study Description(click to expand)DUAL PRIMARY OBJECTIVE: I. To determine disease free survival (DFS) and overall survival (OS) in all patients with muscle-invasive bladder and upper-tract urothelial carcinoma treated with adjuvant pembrolizumab versus (vs.) observation. SECONDARY OBJECTIVES: I. To determine DFS and OS in PD-L1 positive and negative patients with muscle-invasive bladder and upper-tract urothelial carcinoma treated with adjuvant pembrolizumab vs. observation. II. To characterize the safety and tolerability of pembrolizumab when administered in the adjuvant setting in patients with muscle-invasive bladder and upper-tract urothelial carcinoma. CORRELATIVE SCIENCE OBJECTIVES: I. To determine if the 12 immune gene signatures are associated with OS and DFS. II. To determine if tumor molecular subtype is associated with OS and DFS. III. To investigate whether the diversity of T-cell receptor (TCR) clonotypes is associated with OS and DFS. IV. To investigate whether persistence of TCR clonotypes is associated with OS and DFS. V. To determine if tumor burden and neoantigen burden are associated with OS and DFS. VI. To determine if HLA subtypes are associated with OS and DFS. VII. To conduct exploratory analyses regarding the association of plasma HGF and VEGF levels with IL-10 and IL-17 and OS and DFS and between treated and untreated patients. PHARMACOGENOMIC...
DUAL PRIMARY OBJECTIVE:
I. To determine disease free survival (DFS) and overall survival (OS) in all patients with muscle-invasive bladder and upper-tract urothelial carcinoma treated with adjuvant pembrolizumab versus (vs.) observation.
SECONDARY OBJECTIVES:
I. To determine DFS and OS in PD-L1 positive and negative patients with muscle-invasive bladder and upper-tract urothelial carcinoma treated with adjuvant pembrolizumab vs. observation.
II. To characterize the safety and tolerability of pembrolizumab when administered in the adjuvant setting in patients with muscle-invasive bladder and upper-tract urothelial carcinoma.
CORRELATIVE SCIENCE OBJECTIVES:
I. To determine if the 12 immune gene signatures are associated with OS and DFS.
II. To determine if tumor molecular subtype is associated with OS and DFS. III. To investigate whether the diversity of T-cell receptor (TCR) clonotypes is associated with OS and DFS.
IV. To investigate whether persistence of TCR clonotypes is associated with OS and DFS.
V. To determine if tumor burden and neoantigen burden are associated with OS and DFS.
VI. To determine if HLA subtypes are associated with OS and DFS. VII. To conduct exploratory analyses regarding the association of plasma HGF and VEGF levels with IL-10 and IL-17 and OS and DFS and between treated and untreated patients.
PHARMACOGENOMIC STUDY OBJECTIVES:
I. To investigate the effect of PDCD1 single-nucleotide polymorphism (SNP) rs11568821 on severe (grade 3 or higher) immune-related toxicity in the pembrolizumab-treated cohort.
II. To investigate whether other SNPs commonly polymorphic within or near PDCD1 associate with development of pembrolizumab toxicity in the treated cohort.
III. To identify novel germline genetic markers of treatment-related toxicity through genome-wide association analysis of pembrolizumab-treated patients.
IV. To identify novel germline genetic markers that are associated with DFS and OS through genome-wide association analysis.
QUALITY OF LIFE CORRELATIVE STUDY OBJECTIVES:
I. To compare health-related quality of life (HRQL) as assessed by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-core (C)30 between patients randomized to pembrolizumab vs. observation.
II. To compare urinary symptoms as assessed by EORTC QLQ- muscle-invasive bladder cancer module (BLM)30 between patients randomized to pembrolizumab vs. observation.
III. To compare patient-reported fatigue, diarrhea, and pain between patients randomized to pembrolizumab vs. observation.
IV. To compare health utilities and quality-adjusted life year (QALYs) between patients randomized to pembrolizumab vs. observation.
V. To compare other scale scores of the EORTC QLQ-C30, EORTC QLQ-BLM30, and European Quality of Life 5 Dimensions 5 Levels (EQ5D-5L) between patients randomized to pembrolizumab vs. observation.
VI. To compare global quality of life, symptoms, health utilities, QALYs, and other scale scores of the three questionnaires between patients randomized to pembrolizumab vs. observation within subgroups defined by each of the stratification factors.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) scan, CT urography, and/or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo a cystoscopy and blood sample collection during screening and on study.
ARM B: Patients undergo observation. Patients undergo a CT scan, CT urography, and/or MRI throughout the trial. Patients may also undergo a cystoscopy and blood sample collection during screening and on study.
After completion of study treatment, patients are followed up every 12 weeks for up 2 years, and then annually for 10 years.
Status Flow
Change History
96 versions recorded-
Apr 13, 2026 — Present [daily]
Active Not Recruiting
Phase: PHASE3 → None
-
Mar 2026 — Present [monthly]
Active Not Recruiting PHASE3
-
Mar 2026 — Present [monthly]
Active Not Recruiting PHASE3
-
Feb 2026 — Mar 2026 [monthly]
Active Not Recruiting PHASE3
-
Feb 2026 — Present [monthly]
Active Not Recruiting PHASE3
▶ Show 91 earlier versions
-
Jan 2026 — Feb 2026 [monthly]
Active Not Recruiting PHASE3
-
Jan 2026 — Present [monthly]
Active Not Recruiting PHASE3
-
Dec 2025 — Jan 2026 [monthly]
Active Not Recruiting PHASE3
-
Nov 2025 — Dec 2025 [monthly]
Active Not Recruiting PHASE3
-
Sep 2025 — Nov 2025 [monthly]
Active Not Recruiting PHASE3
-
May 2025 — Sep 2025 [monthly]
Active Not Recruiting PHASE3
-
Apr 2025 — May 2025 [monthly]
Active Not Recruiting PHASE3
-
Mar 2025 — Apr 2025 [monthly]
Active Not Recruiting PHASE3
-
Feb 2025 — Mar 2025 [monthly]
Active Not Recruiting PHASE3
-
Jan 2025 — Feb 2025 [monthly]
Active Not Recruiting PHASE3
-
Dec 2024 — Jan 2025 [monthly]
Active Not Recruiting PHASE3
-
Nov 2024 — Dec 2024 [monthly]
Active Not Recruiting PHASE3
-
Oct 2024 — Nov 2024 [monthly]
Active Not Recruiting PHASE3
-
Sep 2024 — Oct 2024 [monthly]
Active Not Recruiting PHASE3
-
Aug 2024 — Sep 2024 [monthly]
Active Not Recruiting PHASE3
-
Jul 2024 — Aug 2024 [monthly]
Active Not Recruiting PHASE3
-
Jun 2024 — Jul 2024 [monthly]
Active Not Recruiting PHASE3
-
May 2024 — Jun 2024 [monthly]
Active Not Recruiting PHASE3
-
Apr 2024 — May 2024 [monthly]
Active Not Recruiting PHASE3
-
Mar 2024 — Apr 2024 [monthly]
Active Not Recruiting PHASE3
-
Feb 2024 — Mar 2024 [monthly]
Active Not Recruiting PHASE3
-
Jan 2024 — Feb 2024 [monthly]
Active Not Recruiting PHASE3
-
Dec 2023 — Jan 2024 [monthly]
Active Not Recruiting PHASE3
-
Nov 2023 — Dec 2023 [monthly]
Active Not Recruiting PHASE3
-
Oct 2023 — Nov 2023 [monthly]
Active Not Recruiting PHASE3
-
Sep 2023 — Oct 2023 [monthly]
Active Not Recruiting PHASE3
-
Aug 2023 — Sep 2023 [monthly]
Active Not Recruiting PHASE3
-
Jul 2023 — Aug 2023 [monthly]
Active Not Recruiting PHASE3
-
Jun 2023 — Jul 2023 [monthly]
Active Not Recruiting PHASE3
-
May 2023 — Jun 2023 [monthly]
Active Not Recruiting PHASE3
-
Apr 2023 — May 2023 [monthly]
Active Not Recruiting PHASE3
-
Mar 2023 — Apr 2023 [monthly]
Active Not Recruiting PHASE3
-
Feb 2023 — Mar 2023 [monthly]
Active Not Recruiting PHASE3
-
Dec 2022 — Feb 2023 [monthly]
Active Not Recruiting PHASE3
-
Nov 2022 — Dec 2022 [monthly]
Active Not Recruiting PHASE3
-
Sep 2022 — Nov 2022 [monthly]
Active Not Recruiting PHASE3
-
Jul 2022 — Sep 2022 [monthly]
Active Not Recruiting PHASE3
-
Jun 2022 — Jul 2022 [monthly]
Active Not Recruiting PHASE3
-
May 2022 — Jun 2022 [monthly]
Active Not Recruiting PHASE3
-
Apr 2022 — May 2022 [monthly]
Active Not Recruiting PHASE3
-
Feb 2022 — Apr 2022 [monthly]
Active Not Recruiting PHASE3
-
Jan 2022 — Feb 2022 [monthly]
Active Not Recruiting PHASE3
-
Dec 2021 — Jan 2022 [monthly]
Active Not Recruiting PHASE3
-
Nov 2021 — Dec 2021 [monthly]
Active Not Recruiting PHASE3
-
Sep 2021 — Nov 2021 [monthly]
Active Not Recruiting PHASE3
Status: Recruiting → Active Not Recruiting
-
Jun 2021 — Sep 2021 [monthly]
Recruiting PHASE3
-
May 2021 — Jun 2021 [monthly]
Recruiting PHASE3
-
Apr 2021 — May 2021 [monthly]
Recruiting PHASE3
-
Mar 2021 — Apr 2021 [monthly]
Recruiting PHASE3
-
Feb 2021 — Mar 2021 [monthly]
Recruiting PHASE3
-
Jan 2021 — Feb 2021 [monthly]
Recruiting PHASE3
-
Dec 2020 — Jan 2021 [monthly]
Recruiting PHASE3
-
Nov 2020 — Dec 2020 [monthly]
Recruiting PHASE3
-
Oct 2020 — Nov 2020 [monthly]
Recruiting PHASE3
-
Sep 2020 — Oct 2020 [monthly]
Recruiting PHASE3
-
Aug 2020 — Sep 2020 [monthly]
Recruiting PHASE3
-
Jul 2020 — Aug 2020 [monthly]
Recruiting PHASE3
-
Jun 2020 — Jul 2020 [monthly]
Recruiting PHASE3
-
May 2020 — Jun 2020 [monthly]
Recruiting PHASE3
-
Apr 2020 — May 2020 [monthly]
Recruiting PHASE3
-
Mar 2020 — Apr 2020 [monthly]
Recruiting PHASE3
-
Feb 2020 — Mar 2020 [monthly]
Recruiting PHASE3
-
Jan 2020 — Feb 2020 [monthly]
Recruiting PHASE3
-
Dec 2019 — Jan 2020 [monthly]
Recruiting PHASE3
-
Nov 2019 — Dec 2019 [monthly]
Recruiting PHASE3
-
Oct 2019 — Nov 2019 [monthly]
Recruiting PHASE3
-
Sep 2019 — Oct 2019 [monthly]
Recruiting PHASE3
-
Aug 2019 — Sep 2019 [monthly]
Recruiting PHASE3
-
Jul 2019 — Aug 2019 [monthly]
Recruiting PHASE3
-
Jun 2019 — Jul 2019 [monthly]
Recruiting PHASE3
-
May 2019 — Jun 2019 [monthly]
Recruiting PHASE3
-
Apr 2019 — May 2019 [monthly]
Recruiting PHASE3
-
Mar 2019 — Apr 2019 [monthly]
Recruiting PHASE3
-
Feb 2019 — Mar 2019 [monthly]
Recruiting PHASE3
-
Jan 2019 — Feb 2019 [monthly]
Recruiting PHASE3
-
Dec 2018 — Jan 2019 [monthly]
Recruiting PHASE3
-
Nov 2018 — Dec 2018 [monthly]
Recruiting PHASE3
-
Oct 2018 — Nov 2018 [monthly]
Recruiting PHASE3
-
Sep 2018 — Oct 2018 [monthly]
Recruiting PHASE3
-
Aug 2018 — Sep 2018 [monthly]
Recruiting PHASE3
-
Jul 2018 — Aug 2018 [monthly]
Recruiting PHASE3
-
Jun 2018 — Jul 2018 [monthly]
Recruiting PHASE3
-
May 2018 — Jun 2018 [monthly]
Recruiting PHASE3
-
Apr 2018 — May 2018 [monthly]
Recruiting PHASE3
-
Mar 2018 — Apr 2018 [monthly]
Recruiting PHASE3
-
Feb 2018 — Mar 2018 [monthly]
Recruiting PHASE3
-
Jan 2018 — Feb 2018 [monthly]
Recruiting PHASE3
-
Dec 2017 — Jan 2018 [monthly]
Recruiting PHASE3
-
Nov 2017 — Dec 2017 [monthly]
Recruiting PHASE3
-
Oct 2017 — Nov 2017 [monthly]
Recruiting PHASE3
Status: Not Yet Recruiting → Recruiting
-
Aug 2017 — Oct 2017 [monthly]
Not Yet Recruiting PHASE3
First recorded
Eligibility Summary
This phase III trial studies how well pembrolizumab works in treating patients with bladder cancer that has spread into the deep muscle of the bladder wall (muscle-invasive) or urothelial cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Monoclonal antibodies recognizing and blocking checkpoint molecules can enhance the patient's immune response and therefore help fight cancer. Pembrolizumab is one of the monoclonal antibodies that block the PD-1 axis and can interfere with the ability of tumor cells to grow.
Contact Information
- National Cancer Institute (NCI)
For direct contact, visit the study record on ClinicalTrials.gov .