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

NCT ID: NCT03123055

Last Updated: 2020-03-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-20
• Study Completion Date: 2019-12-01

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

B-701

Intervention Type: DRUG

B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.

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.

Group Type: EXPERIMENTAL

B-701

Intervention Type: DRUG

B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.

Pembrolizumab

Intervention Type: DRUG

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.

Interventions

B-701

B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

MFGR1877S; Vofatamab; Keytruda

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rainier Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainier Therapeutics

Role: STUDY_CHAIR

Rainier Therapeutics

Locations

Research Site

Greenbrae, California, United States

Research Site

Fort Wayne, Indiana, United States

Research Site

Louisville, Kentucky, United States

Washington University School of Medicine

St Louis, Missouri, United States

Research Site

Cleveland, Ohio, United States

Research Site

Philadelphia, Pennsylvania, United States

Research Site

Germantown, Tennessee, United States

Research Site

Houston, Texas, United States

Research Site

Brussels, , Belgium

Research Site

Leuven, , Belgium

Research Team

Yvoir, , Belgium

Research Team

Copenhagen, , Denmark

Research Site

Bordeaux, , France

Research Site

Dijon, , France

Research Site

Dresden, , Germany

Research Site

Frankfurt, , Germany

Research Site

Heidelberg, , Germany

Research Site

Kassel, , Germany

Research Site

Munich, , Germany

Research Site

Münster, , Germany

Research Site

Budapest, , Hungary

Research Site

Milan, , Italy

Research Site

Milan, , Italy

Research Site

Chisinau, , Moldova

Research Site

Utrecht, , Netherlands

Research Site

Katowice, , Poland

Research Site

Warsaw, , Poland

Research Site

Warsaw, , Poland

Research Site

Wieliszew, , Poland

Research Site

Wroclaw, , Poland

Research Site

Moscow, , Russia

Research Site

Saint Petersburg, , Russia

Research Team

Ufa, , Russia

Research Site

Belgrade, , Serbia

Research Site

Belgrade, , Serbia

Research Site

Kamenitz, , Serbia

Research Site

Kragujevac, , Serbia

Research Site

Niš, , Serbia

Research Site

Gwangju, , South Korea

Research Site

Seongnam-si, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Madrid, CA, Spain

Research Site

Barcelona, , Spain

Research Site

Barcelona, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Research Site

Uppsala, , Sweden

Research Site

Ankara, , Turkey (Türkiye)

Research Site

Antalya, , Turkey (Türkiye)

Research Site

Dnipro, , Ukraine

Research Site

Kyiv, , Ukraine

Countries

United States; Belgium; Denmark; France; Germany; Hungary; Italy; Moldova; Netherlands; Poland; Russia; Serbia; South Korea; Spain; Sweden; Turkey (Türkiye); Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-001292-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B-701-U22

Identifier Type: -

Identifier Source: org_study_id