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Trial record 1 of 1 for:    NCT03123055
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A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma (FIERCE-22)

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ClinicalTrials.gov Identifier: NCT03123055
Recruitment Status : Recruiting
First Posted : April 21, 2017
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Rainier Therapeutics

Tracking Information
First Submitted Date  ICMJE April 11, 2017
First Posted Date  ICMJE April 21, 2017
Last Update Posted Date January 16, 2019
Actual Study Start Date  ICMJE April 20, 2017
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Initial safety and determination of recommended Phase 2 dose according to dose-limiting Toxicity [ Time Frame: 1 year ]
    DLTs 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.
  • Safety and tolerability of B-701 (vofatamab) plus pembrolizumab [ 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.
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • Evaluate FGFR3 Expression [ Time Frame: 2 years ]
    To evaluate the association between FGFR3 receptor expression and the expression of markers of FGFR3 pathway inhibition within each molecular subtype and across four subtypes (i.e., luminal 1, luminal 2, basal 1, and basal 2) following treatment with B-701 alone.
  • Safety and Tolerability assessed through summaries of AEs [ Time Frame: 2 years ]
    Evaluate the safety and tolerability of B-701 plus atezolizumab in subjects with UCC as measured by AEs.
  • Safety and Tolerability assessed through summaries of physical examination findings. [ Time Frame: 2 years ]
    Evaluate the safety and tolerability of B-701 plus atezolizumab in subjects with UCC as measured by physical examinations.
  • Safety and Tolerability assessed through summaries of laboratory test results. [ Time Frame: 2 years ]
    Evaluate the safety and tolerability of B-701 plus atezolizumab in subjects with UCC as measured by laboratory results.
  • Safety and Tolerability assessed through summaries of vital signs. [ Time Frame: 2 years ]
    Evaluate the safety and tolerability of B-701 plus atezolizumab in subjects with UCC as measured by vital signs.
Change History Complete list of historical versions of study NCT03123055 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • Efficacy of B-701 in Combination with Atezolizumab as measured by ORR [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 in combination with atezolizumab in the treatment of subjects with UCC as measured by objective response rate (ORR)
  • Efficacy of B-701 in Combination with Atezolizumab as measured by OS [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 in combination with atezolizumab in the treatment of subjects with UCC as measured by overall survival (OS)
  • Efficacy of B-701 in Combination with Atezolizumab as measured by PFS [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 in combination with atezolizumab in the treatment of subjects with UCC as measured by progression-free survival (PFS)
  • Efficacy of B-701 in Combination with Atezolizumab as measured by DCR [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 in combination with atezolizumab in the treatment of subjects with UCC as measured by disease control rate (DCR)
  • Efficacy of B-701 in Combination with Atezolizumab as measured by DOR [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 in combination with atezolizumab in the treatment of subjects with UCC as measured by duration of objective response (DOR).
  • Evaluate the pharmacokinetics (PK) of B-701 in subjects with UCC [ Time Frame: 2 years ]
    B-701 levels will be compared to those observed in previous studies to ensure that the combination of B-701 plus atezolizumab neither increases nor decreases predicted B-701 levels and drug exposure is consistent with what was previously observed.
  • Evaluate the pharmacokinetics (PK) of B-701 in subjects with UCC (Cmax) [ Time Frame: 2 years ]
    At several time points throughout the study approximate Cmax will be determined
  • Evaluate the pharmacokinetics (PK) of B-701 in subjects with UCC (Cmin) [ Time Frame: 2 years ]
    At several time points throughout the study Cmin will be determined
  • Assess Immunogenicity of B-701 as measured by anti-B-701 antibody titers [ Time Frame: 2 years ]
    Assess the immunogenicity of B-701 in subjects with UCC by determining whether antibodies to B-701 are generated in subjects on trial.
  • Tumor Marker Evaluation as measured by gene or protein expression [ Time Frame: 2 years ]
    Expression of immune surveillance in markers as measured by gene or protein expression will be evaluated for proportionate change from baseline to post-B-701 treatment and compared to tumor sub-type and genetic background.
  • Tumor Marker Evaluation [ Time Frame: 2 years ]
    IHC outcomes will be assessed for increase or decrease relative to baseline and compared to tumor sub-type and genetic background.
  • Evaluation of Genetic Markers Predictive of B-701 Response [ Time Frame: 2 years ]
    A panel of cancer-related genes, including FGFR3, will be evaluated for genetic changes that may help to identify the characteristics of tumors that are most likely to respond to B-701 treatment.
Current Other Pre-specified Outcome Measures
 (submitted: January 11, 2019)
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Locally Advanced or Metastatic Urothelial Cell Carcinoma
  • Urinary Bladder Disease
  • Urological Diseases
Intervention  ICMJE
  • Drug: B-701
    B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.
    Other Names:
    • MFGR1877S
    • Vofatamab
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: B-701
  • 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.
    Interventions:
    • Drug: B-701
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 24, 2018)
74
Original Estimated Enrollment  ICMJE
 (submitted: April 20, 2017)
48
Estimated Study Completion Date  ICMJE September 30, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. 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.
  2. Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
  3. 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.
  4. Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.

Key Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Primary central nervous system (CNS) malignancy or CNS metastases.
  5. History of clinically significant coagulation or platelet disorder in the past 12 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rainier Therapeutics 925-413-6140 clin-ops@rainierrx.com
Listed Location Countries  ICMJE Belgium,   Denmark,   France,   Germany,   Hungary,   Italy,   Korea, Republic of,   Moldova, Republic of,   Netherlands,   Poland,   Russian Federation,   Serbia,   Spain,   Sweden,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03123055
Other Study ID Numbers  ICMJE B-701-U22
2017-001292-23 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rainier Therapeutics
Study Sponsor  ICMJE Rainier Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Rainier Therapeutics Rainier Therapeutics
PRS Account Rainier Therapeutics
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP