Back to resultsA Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma (FIERCE-22)
Primary Purpose
Locally Advanced or Metastatic Urothelial Cell Carcinoma, Urinary Bladder Disease, Urological Diseases
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
B-701
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced or Metastatic Urothelial Cell Carcinoma focused on measuring Urothelial Cell Carcinoma, UCC, bladder cancer, B-701, FGFR3, invasive bladder cancer, Transitional Cell Carcinoma, TCC, second line therapy, monoclonal antibody, combination therapy, Phase 1b, pembrolizumab, checkpoint inhibitor, Phase 2, Urothelial Carcinoma, Vofatamab
Eligibility Criteria
Key Inclusion Criteria:
- Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
- Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
- Have available archival tumor or be willing to undergo diagnostic biopsy at screening. Sample must be of suitable quality and quantity to satisfy group assignment and biomarker endpoints.
- Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
Key Exclusion Criteria:
- Participants with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest CT scan.
- Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor or FGFR inhibitor.
- Patients with autoimmune disease or medical conditions that required systemic corticosteroids (> 10 mg/day prednisone or its equivalent) or other immunosuppressive medications or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment. Note: Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Primary central nervous system (CNS) malignancy or CNS metastases.
- History of clinically significant coagulation or platelet disorder in the past 12 months.
Sites / Locations
- Research Site
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- Research Site
- Washington University School of Medicine
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- Research Team
- Research Team
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- Research Team
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
B-701 (vofatamab)
B-701 (vofatamab) plus pembrolizumab
Arm Description
B-701 (vofatamab, 25 mg/kg) will be administered via IV infusion on Cycle 0 Day 1 for a single 14-day cycle.
B-701 (vofatamab, 25 mg/kg [or the recommended Phase 2 dose if different than 25 mg/kg]) plus pembrolizumab (200 mg) will be administered by IV infusion on Cycle 1 Day 1 once every 3 weeks.
Outcomes
Primary Outcome Measures
Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days
Number of Participants with Dose Limiting Toxicities within a period of 35 days will be analyzed reviewing the aggregate of adverse events (AEs) and serious adverse events (SAEs) by the B-701 program Safety Oversight Committee and will result in a recommended Phase 2 dose. Six subjects at a time are enrolled and observed for 35 days after the initial dose. If 2 or more subjects experience a DLT that dose will be declared intolerable and de-escalation of the dose will occur.
Number of Subjects Experiencing Adverse Events (AEs and SAEs)
Evaluate the safety and tolerability of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as assessed by number of subjects experiencing adverse events (AEs and SAEs), physical examination findings, laboratory test results, and vital signs over time. This outcome is measured by a safety monitoring committee who regularly met and reviewed aggregate trends of reports AEs, lab ranges, physical exams etc. and determined if the drug was safe to continue.
Efficacy of B-701 (Vofatamab) Plus Pembrolizumab Measured by ORR
Evaluate the efficacy of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as measured by objective response rate (ORR) by RECIST 1.1. ORR is defined as the percentage of subjects who have baseline measurable disease and who achieve a best response of either complete response (CR) or partial response (PR).
Secondary Outcome Measures
Assessment of Changes in Biomarkers Induced by B-701 (Vofatamab)
Whole blood (PBMCs), serum, and plasma samples for biomarker analyses will be obtained prior to infusion of B-701 at pre-defined visit days.
The effects of B-701 on the downstream signaling of the FGFR3 pathway, tumor sub-type and on the immune surveillance of UCC tumors will be monitored using techniques that include gene expression profiling (such as whole transcriptome RNAseq), sequencing of T-cell receptors, and immunohistochemistry.
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DOR
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by duration of objective response (DOR), defined as the time from first occurrence of a documented, objective response until the time of relapse or death from any cause (RECIST 1.1).
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DCR
Evaluate the efficacy of B-701 in combination with pembrolizumab in the treatment of subjects with UCC as measured by disease control rate (DCR), defined as the percentage of subjects who achieve either complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST 1.1.
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by PFS
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by progression-free survival (PFS), defined as the time from a first study treatment dose to first occurrence of disease progression (per RECIST 1.1) or death from any cause, whichever occurs first.
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by OS
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by overall survival (OS), defined as the time from first study drug administration to death from any cause (RECIST 1.1)
Change in Subject Reported Quality of Life
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by the change over time in subject reported quality of life as measured by the European Organization for Research and Treatment Quality of Life Questionnaire (EORTC QLQ-C30).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03123055
Brief Title
A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
Acronym
FIERCE-22
Official Title
A Multi-Center, Open-Label Phase 1b/2 Study of a Novel FGFR3 Inhibitor (B-701) Combined With Pembrolizumab in Subjects With Locally Advanced or Metastatic Urothelial Carcinoma Who Have Progressed Following Platinum-based Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
program has been put on hold by the sponsor
Study Start Date
April 20, 2017 (Actual)
Primary Completion Date
December 1, 2019 (Actual)
Study Completion Date
December 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rainier Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1b/2 multi-center, open-label study to establish the initial safety and to determine a recommended Phase 2 dose of B-701 in combination with pembrolizumab, and to determine safety, tolerability and efficacy of B-701 (vofatamab) plus pembrolizumab in the treatment of subjects with locally advanced or metastatic UCC, who have progressed following platinum-based chemotherapy and who have not received prior immune checkpoint inhibitor therapy.
Detailed Description
This is a Phase 1b/2 multi-center, open-label study to determine the safety, tolerability, and efficacy of B-701 (vofatamab) plus pembrolizumab in the treatment of subjects with locally advanced or metastatic UCC, who have progressed following platinum-based chemotherapy and who have not received prior immune checkpoint inhibitor or FGFR inhibitor-targeted therapy. The study consists of 2 parts: a Phase 1b lead-in phase enrolling 6 to 18 subjects and a Phase 2 dose expansion phase enrolling up to a total of 74 subjects.
Subjects who discontinue B-701 (vofatamab) may continue on study and receive pembrolizumab alone until disease progression, death, withdrawal of patient consent, or study termination. Subjects who discontinue pembrolizumab may continue on study and receive B-701 (vofatamab) alone until disease progression, death, withdrawal of patient consent, or study termination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced or Metastatic Urothelial Cell Carcinoma, Urinary Bladder Disease, Urological Diseases
Keywords
Urothelial Cell Carcinoma, UCC, bladder cancer, B-701, FGFR3, invasive bladder cancer, Transitional Cell Carcinoma, TCC, second line therapy, monoclonal antibody, combination therapy, Phase 1b, pembrolizumab, checkpoint inhibitor, Phase 2, Urothelial Carcinoma, Vofatamab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
B-701 (vofatamab) as monotherapy for first 2 weeks followed by B-701 (vofatamab) in combination with pembrolizumab thereafter.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
B-701 (vofatamab)
Arm Type
Experimental
Arm Description
B-701 (vofatamab, 25 mg/kg) will be administered via IV infusion on Cycle 0 Day 1 for a single 14-day cycle.
Arm Title
B-701 (vofatamab) plus pembrolizumab
Arm Type
Experimental
Arm Description
B-701 (vofatamab, 25 mg/kg [or the recommended Phase 2 dose if different than 25 mg/kg]) plus pembrolizumab (200 mg) will be administered by IV infusion on Cycle 1 Day 1 once every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
B-701
Other Intervention Name(s)
MFGR1877S, Vofatamab
Intervention Description
B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab is a humanized antibody used in cancer immunotherapy. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days
Description
Number of Participants with Dose Limiting Toxicities within a period of 35 days will be analyzed reviewing the aggregate of adverse events (AEs) and serious adverse events (SAEs) by the B-701 program Safety Oversight Committee and will result in a recommended Phase 2 dose. Six subjects at a time are enrolled and observed for 35 days after the initial dose. If 2 or more subjects experience a DLT that dose will be declared intolerable and de-escalation of the dose will occur.
Time Frame
1 year
Title
Number of Subjects Experiencing Adverse Events (AEs and SAEs)
Description
Evaluate the safety and tolerability of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as assessed by number of subjects experiencing adverse events (AEs and SAEs), physical examination findings, laboratory test results, and vital signs over time. This outcome is measured by a safety monitoring committee who regularly met and reviewed aggregate trends of reports AEs, lab ranges, physical exams etc. and determined if the drug was safe to continue.
Time Frame
2.5 years
Title
Efficacy of B-701 (Vofatamab) Plus Pembrolizumab Measured by ORR
Description
Evaluate the efficacy of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as measured by objective response rate (ORR) by RECIST 1.1. ORR is defined as the percentage of subjects who have baseline measurable disease and who achieve a best response of either complete response (CR) or partial response (PR).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Assessment of Changes in Biomarkers Induced by B-701 (Vofatamab)
Description
Whole blood (PBMCs), serum, and plasma samples for biomarker analyses will be obtained prior to infusion of B-701 at pre-defined visit days.
The effects of B-701 on the downstream signaling of the FGFR3 pathway, tumor sub-type and on the immune surveillance of UCC tumors will be monitored using techniques that include gene expression profiling (such as whole transcriptome RNAseq), sequencing of T-cell receptors, and immunohistochemistry.
Time Frame
2.5 years
Title
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DOR
Description
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by duration of objective response (DOR), defined as the time from first occurrence of a documented, objective response until the time of relapse or death from any cause (RECIST 1.1).
Time Frame
2 years
Title
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DCR
Description
Evaluate the efficacy of B-701 in combination with pembrolizumab in the treatment of subjects with UCC as measured by disease control rate (DCR), defined as the percentage of subjects who achieve either complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST 1.1.
Time Frame
2 years
Title
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by PFS
Description
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by progression-free survival (PFS), defined as the time from a first study treatment dose to first occurrence of disease progression (per RECIST 1.1) or death from any cause, whichever occurs first.
Time Frame
2 years
Title
Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by OS
Description
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by overall survival (OS), defined as the time from first study drug administration to death from any cause (RECIST 1.1)
Time Frame
2.5 years
Title
Change in Subject Reported Quality of Life
Description
Evaluate the efficacy of B-701 (vofatamab) in combination with pembrolizumab in the treatment of subjects with UCC as measured by the change over time in subject reported quality of life as measured by the European Organization for Research and Treatment Quality of Life Questionnaire (EORTC QLQ-C30).
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
PK Analysis of B-701 (Vofatamab)
Description
PK will be analyzed by measuring B-701 C(trough) levels. B-701 C(trough) levels then will be summarized over time throughout the study and will be compared to predicted B-701 C(trough) levels, whose prediction is based on data observed in previous studies with B-701.
Time Frame
2 years
Title
Immunogenicity of B-701 (Vofatamab)
Description
Determine the immunogenicity of B-701 as measured by anti-B-701 antibody titers at several time points throughout the study.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Have available archival tumor or be willing to undergo diagnostic biopsy at screening. Sample must be of suitable quality and quantity to satisfy group assignment and biomarker endpoints.
Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
Key Exclusion Criteria:
Participants with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest CT scan.
Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor or FGFR inhibitor.
Patients with autoimmune disease or medical conditions that required systemic corticosteroids (> 10 mg/day prednisone or its equivalent) or other immunosuppressive medications or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment. Note: Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Primary central nervous system (CNS) malignancy or CNS metastases.
History of clinically significant coagulation or platelet disorder in the past 12 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rainier Therapeutics
Organizational Affiliation
Rainier Therapeutics
Official's Role
Study Chair
Facility Information:
Facility Name
Research Site
City
Greenbrae
State/Province
California
ZIP/Postal Code
94904
Country
United States
Facility Name
Research Site
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
Facility Name
Research Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Research Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Brussel
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Team
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Research Team
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Research Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Research Site
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Name
Research Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Research Site
City
Frankfurt
ZIP/Postal Code
60488
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Research Site
City
Kassel
ZIP/Postal Code
34125
Country
Germany
Facility Name
Research Site
City
Munich
ZIP/Postal Code
81377
Country
Germany
Facility Name
Research Site
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
Research Site
City
Gwangju
ZIP/Postal Code
61469
Country
Korea, Republic of
Facility Name
Research Site
City
Seongnam-si
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Research Site
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Research Site
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-514
Country
Poland
Facility Name
Research Site
City
Warsaw
ZIP/Postal Code
02-567
Country
Poland
Facility Name
Research Site
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Research Site
City
Wieliszew
ZIP/Postal Code
05-135
Country
Poland
Facility Name
Research Site
City
Wroclaw
ZIP/Postal Code
53-413
Country
Poland
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Research Team
City
Ufa
ZIP/Postal Code
450000
Country
Russian Federation
Facility Name
Research Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Research Site
City
Belgrade
ZIP/Postal Code
11070
Country
Serbia
Facility Name
Research Site
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
Research Site
City
Niš
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Research Site
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
Research Site
City
Madrid
State/Province
CA
ZIP/Postal Code
28050
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Research Site
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Research Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Research Site
City
Antalya
ZIP/Postal Code
07059
Country
Turkey
Facility Name
Research Site
City
Dnipropetrovs'k
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Research Site
City
Kiew
ZIP/Postal Code
03022
Country
Ukraine
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
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