Clinical Trials /

A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma

NCT03123055

Description:

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.

Related Conditions:
  • Transitional Cell Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: B-701-U22
  • SECONDARY ID: 2017-001292-23
  • NCT ID: NCT03123055

Conditions

  • Locally Advanced or Metastatic Urothelial Cell Carcinoma
  • Urinary Bladder Disease
  • Urological Diseases

Interventions

DrugSynonymsArms
B-701MFGR1877S, VofatamabB-701 (vofatamab)
PembrolizumabKeytrudaB-701 (vofatamab) plus pembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
B-701 (vofatamab)ExperimentalB-701 (vofatamab, 25 mg/kg) will be administered via IV infusion on Cycle 0 Day 1 for a single 14-day cycle.
  • B-701
B-701 (vofatamab) plus pembrolizumabExperimentalB-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.
  • B-701
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Initial safety and determination of recommended Phase 2 dose according to dose-limiting Toxicity
Time Frame:1 year
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Assessment of changes in biomarkers induced by B-701 (vofatamab)
Time Frame:2.5 years
Safety Issue:
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.
Measure:Efficacy of B-701 (vofatamab) in combination with pembrolizumab as measured by DOR
Time Frame:2 years
Safety Issue:
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).
Measure:Efficacy of B-701 (vofatamab) in combination with pembrolizumab as measured by DCR
Time Frame:2 years
Safety Issue:
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.
Measure:Efficacy of B-701 (vofatamab) in combination with pembrolizumab as measured by PFS
Time Frame:2 years
Safety Issue:
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.
Measure:Efficacy of B-701 (vofatamab) in combination with pembrolizumab as measured by OS
Time Frame:2.5 years
Safety Issue:
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)
Measure:Change in subject reported quality of life
Time Frame:2 years
Safety Issue:
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).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Rainier Therapeutics

Trial 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

Last Updated

December 9, 2019