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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 : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
BioClin Therapeutics, Inc.

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 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

Detailed Description:

This is a Phase 1b/2 multi-center, open-label study to determine the safety, tolerability, and efficacy of B-701 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 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 alone until disease progression, death, withdrawal of patient consent, or study termination.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: B-701 as monotherapy for first 2 weeks followed by B-701 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
Estimated Primary Completion Date : December 30, 2018
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: B-701
B-701 (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 is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.
Other Name: MFGR1877S

Experimental: B-701 plus pembrolizumab
B-701 (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 is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.
Other Name: MFGR1877S

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 :
  1. 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.

  2. Safety and tolerability of B-701 plus pembrolizumab [ Time Frame: 2.5 years ]
    Evaluate the safety and tolerability of B-701 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.

  3. Efficacy of B-701 plus pembrolizumab measured by ORR [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 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 :
  1. Assessment of changes in biomarkers induced by B-701 [ 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.


  2. Efficacy of B-701 in combination with pembrolizumab as measured by DOR [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 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).

  3. Efficacy of B-701 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.

  4. Efficacy of B-701 in combination with pembrolizumab as measured by PFS [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 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.

  5. Efficacy of B-701 in combination with pembrolizumab as measured by OS [ Time Frame: 2.5 years ]
    Evaluate the efficacy of B-701 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)

  6. Change in subject reported quality of life [ Time Frame: 2 years ]
    Evaluate the efficacy of B-701 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:
  1. PK analysis of B-701 [ 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.

  2. Immunogenicity of B-701 [ 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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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


Contacts
Contact: BioClin Therapeutics 925-413-6140 clin-ops@bioclintherapeutics.com

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Sponsors and Collaborators
BioClin Therapeutics, Inc.
Investigators
Study Chair: BioClin Therapeutics Sponsor GmbH

Responsible Party: BioClin Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03123055     History of Changes
Other Study ID Numbers: B-701-U22
2017-001292-23 ( EudraCT Number )
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
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 BioClin Therapeutics, Inc.:
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

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Antibodies
Antibodies, Monoclonal
Pembrolizumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents