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

Locally Advanced or Metastatic Urothelial Cell Carcinoma Clinical Trial

— FIERCE-22  

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03123055
• Other study ID #: B-701-U22
• Secondary ID: 2017-001292-23
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 20, 2017
• Est. completion date: December 1, 2019

Study information

• Verified date: February 2020
• Source: Rainier Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Belgium	Research Site	Brussel
Belgium	Research Site	Leuven
Belgium	Research Team	Yvoir
Denmark	Research Team	Copenhagen
France	Research Site	Bordeaux
France	Research Site	Dijon
Germany	Research Site	Dresden
Germany	Research Site	Frankfurt
Germany	Research Site	Heidelberg
Germany	Research Site	Kassel
Germany	Research Site	Munich
Germany	Research Site	Münster
Hungary	Research Site	Budapest
Italy	Research Site	Milano
Italy	Research Site	Milano
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Moldova, Republic of	Research Site	Chisinau
Netherlands	Research Site	Utrecht
Poland	Research Site	Katowice
Poland	Research Site	Warsaw
Poland	Research Site	Warsaw
Poland	Research Site	Wieliszew
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Team	Ufa
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Kragujevac
Serbia	Research Site	Niš
Serbia	Research Site	Sremska Kamenica
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid	CA
Sweden	Research Site	Uppsala
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Ukraine	Research Site	Dnipropetrovs'k
Ukraine	Research Site	Kiew
United States	Research Site	Cleveland	Ohio
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Germantown	Tennessee
United States	Research Site	Greenbrae	California
United States	Research Site	Houston	Texas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Rainier Therapeutics

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Moldova, Republic of,  Netherlands,  Poland,  Russian Federation,  Serbia,  Spain,  Sweden,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PK Analysis of B-701 (Vofatamab)	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 years
Other	Immunogenicity of B-701 (Vofatamab)	Determine the immunogenicity of B-701 as measured by anti-B-701 antibody titers at several time points throughout the study.	2 years
Primary	Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days	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.	1 year
Primary	Number of Subjects Experiencing Adverse Events (AEs and SAEs)	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.	2.5 years
Primary	Efficacy of B-701 (Vofatamab) Plus Pembrolizumab Measured by ORR	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).	2 years
Secondary	Assessment of Changes in Biomarkers Induced by B-701 (Vofatamab)	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.	2.5 years
Secondary	Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DOR	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).	2 years
Secondary	Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DCR	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.	2 years
Secondary	Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by PFS	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.	2 years
Secondary	Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by OS	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)	2.5 years
Secondary	Change in Subject Reported Quality of Life	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).	2 years