Trial record 1 of 1 for:
B-701-U22
A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma (FIERCE-22)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03123055 |
|
Recruitment Status :
Terminated
(program has been put on hold by the sponsor)
First Posted : April 21, 2017
Results First Posted : March 18, 2020
Last Update Posted : March 18, 2020
|
Sponsor:
Rainier Therapeutics
Information provided by (Responsible Party):
Rainier Therapeutics
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Locally Advanced or Metastatic Urothelial Cell Carcinoma Urinary Bladder Disease Urological Diseases | Drug: B-701 Drug: Pembrolizumab | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 28 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention 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) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | April 20, 2017 |
| Actual Primary Completion Date : | December 1, 2019 |
| Actual Study Completion Date : | December 1, 2019 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
|
Experimental: B-701 (vofatamab)
B-701 (vofatamab, 25 mg/kg) will be administered via IV infusion on Cycle 0 Day 1 for a single 14-day cycle.
|
Drug: B-701
B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.
Other Names:
|
|
Experimental: B-701 (vofatamab) plus pembrolizumab
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.
|
Drug: B-701
B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.
Other Names:
Drug: Pembrolizumab 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.
Other Name: Keytruda |
Primary Outcome Measures :
- Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days [ Time Frame: 1 year ]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) [ Time Frame: 2.5 years ]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 [ Time Frame: 2 years ]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) [ Time Frame: 2.5 years ]
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 [ Time Frame: 2 years ]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 [ Time Frame: 2 years ]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 [ Time Frame: 2 years ]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 [ Time Frame: 2.5 years ]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 [ Time Frame: 2 years ]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).
Other Outcome Measures:
- PK Analysis of B-701 (Vofatamab) [ Time Frame: 2 years ]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.
- Immunogenicity of B-701 (Vofatamab) [ Time Frame: 2 years ]Determine the immunogenicity of B-701 as measured by anti-B-701 antibody titers at several time points throughout the study.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03123055
Locations
Show 52 study locations
Sponsors and Collaborators
Rainier Therapeutics
Investigators
| Study Chair: | Rainier Therapeutics | Rainier Therapeutics |
Study Documents (Full-Text)
Documents provided by Rainier Therapeutics:
Documents provided by Rainier Therapeutics:
Study Protocol and Statistical Analysis Plan [PDF] July 1, 2019
| Responsible Party: | Rainier Therapeutics |
| ClinicalTrials.gov Identifier: | NCT03123055 |
| Other Study ID Numbers: |
B-701-U22 2017-001292-23 ( EudraCT Number ) |
| First Posted: | April 21, 2017 Key Record Dates |
| Results First Posted: | March 18, 2020 |
| Last Update Posted: | March 18, 2020 |
| Last Verified: | February 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Rainier Therapeutics:
|
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 |
Additional relevant MeSH terms:
|
Carcinoma Urinary Bladder Diseases Urologic Diseases Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications |
Urogenital Diseases Male Urogenital Diseases Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |