Phase 3
Completed N=700
A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100)
Urothelial Cancer
Source: ClinicalTrials.gov NCT02603432 ↗
Enrolled (actual)
700
Serious AEs
26.7%
Results posted
Dec 2020
Primary outcomePrimary: Overall Survival (OS) — 21.4; 14.3 months — p=0.0005
◆ Published Evidence
Highly cited
212citations · ~71 / year
Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up.
Summary
The main purpose of this study is to compare maintenance treatment with avelumab plus best supportive care (BSC) with BSC alone, to determine if avelumab has an effect on survival in patients with locally advanced or metastatic urothelial cancer that did not worsen during or following completion of first-line chemotherapy.
Linked Publications (5)
-
Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up.
-
Avelumab First-line Maintenance Therapy for Advanced Urothelial Carcinoma: Comprehensive Clinical Subgroup Analyses from the JAVELIN Bladder 100 Phase 3 Trial.
-
Avelumab first-line maintenance plus best supportive care (BSC) vs. BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Asian subgroup analysis.
-
Evaluating Real-World Characteristics of Patients With Advanced Urothelial Carcinoma Eligible for Avelumab Maintenance Therapy: A Multicountry Retrospective Medical Chart Review.
-
Application of statistical machine learning in biomarker selection.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) |
21.4; 14.3 | 0.0005 sig |
| SECONDARY Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) |
3.7; 2.0 | — |
| SECONDARY Progression-Free Survival (PFS) as Assessed by Investigator |
5.5; 2.1 | — |
| SECONDARY Percentage of Participants With Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR) |
9.7; 1.4 | — |
| SECONDARY Percentage of Participants With Objective Response as Assessed by Investigator |
12.3; 3.4 | — |
| SECONDARY Time to Tumor Response (TTR) as Assessed by Blinded Independent Central Review (BICR) |
2.0; 2.0 | — |
| SECONDARY Time to Tumor Response (TTR) as Assessed by Investigator |
2.0; 1.9 | — |
| SECONDARY Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR) |
NA; NA | — |
| SECONDARY Duration of Response (DOR) as Assessed by Investigator |
25.6; NA | — |
| SECONDARY Percentage of Participants With Disease Control (DC) as Assessed by Blinded Independent Central Review (BICR) |
41.1; 27.4 | — |
| SECONDARY Percentage of Participants With Disease Control (DC) as Assessed by Investigator |
50.9; 34.0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 |
37; 76; 113; 104; 163; 58 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3 (G3), Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 |
16; 12; 3; 1; 20; 11 | — |
| SECONDARY Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit |
75.7; 77.0; -0.9; -0.0; -1.7; -1.6 | — |
| SECONDARY Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit |
76.1; 77.1; 0.3; 0.1; -0.2; -0.4 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Avelumab |
192.7; 216.2; 201.5; 208.5; 213.1; 213.1 | — |
| SECONDARY Predose Plasma Concentration (Ctrough) of Avelumab |
3.1; 22.2; 25.2; 26.5; 26.4; 25.7 | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status |
278; 66 | — |
| SECONDARY Number of ADA Ever Positive Participants For Each Serum of ADA Titers for Avelumab |
4; 14; 19; 10; 11; 7 | — |
| SECONDARY Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never Positive and Ever Positive Status |
284; 60 | — |
| SECONDARY Number of Participants With Programmed Death Receptor-1 Ligand 1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) |
189; 169; 139; 131; 22; 50 | — |
| SECONDARY Number of Participants With Cluster of Differentiation 8 (CD8) T Lymphocytes (Cytotoxic T Lymphocytes) |
148; 134 | — |
| SECONDARY Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Score at Day 1 of Cycle 6 |
53.3; 52.7; 1.0; 1.6 | — |
| SECONDARY Time to Deterioration (TTD) Based on National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores |
NA; 13.8 | 0.9130 |
| SECONDARY Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score at Cycle 6 |
0.814; 0.792; -0.029; -0.020 | — |
| SECONDARY Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) - Visual Analog Scale (VAS) Score at Cycle 6 |
74.9; 74.9; 1.6; 0.2 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium
- Stage IV disease at the start of first-line chemotherapy
- Measurable disease (per RECIST v1.1) prior to the start of first-line chemotherapy
- Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin
- No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )
Exclusion Criteria
- Prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization
- Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Persisting toxicity related to prior therapy (Grade >1 NCI CTCAE v4.0); however, alopecia, sensory neuropathy (Grade 2 or less), or other (Grade 2 or less) adverse events not constituting a safety risk based on the investigator's judgement are acceptable.
- Patients with known symptomatic central nervous system (CNS) metastases requiring steroids
- Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.
Data sourced from ClinicalTrials.gov (NCT02603432) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.