Clinical trial NCT03123055: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Locally Advanced or Metastatic Urothelial Cell Carcinoma
Urinary Bladder Disease
Urological Diseases
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
Lead sponsor: Rainier Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: B-701 (vofatamab) as monotherapy for first 2 weeks followed by B-701 (vofatamab) in combination with pembrolizumab thereafter.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days
timeFrame: 1 year
measure: Number of Subjects Experiencing Adverse Events (AEs and SAEs)
timeFrame: 2.5 years
measure: Efficacy of B-701 (Vofatamab) Plus Pembrolizumab Measured by ORR
timeFrame: 2 years
Secondary outcomes:
measure: Assessment of Changes in Biomarkers Induced by B-701 (Vofatamab)
timeFrame: 2.5 years
measure: Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DOR
timeFrame: 2 years
measure: Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DCR
timeFrame: 2 years
measure: Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by PFS
timeFrame: 2 years
measure: Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by OS
timeFrame: 2.5 years
measure: Change in Subject Reported Quality of Life
timeFrame: 2 years
Other outcomes:
measure: PK Analysis of B-701 (Vofatamab)
timeFrame: 2 years
measure: Immunogenicity of B-701 (Vofatamab)
timeFrame: 2 years
Locations:
city: Greenbrae
country: United States
facility: Research Site
state: California
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Brussel
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Team
city: Copenhagen
country: Denmark
facility: Research Team
city: Bordeaux
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Munich
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Chisinau
country: Moldova, Republic of
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Wieliszew
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Team
city: Belgrade
country: Serbia
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Niš
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
state: CA
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Dnipropetrovs'k
country: Ukraine
facility: Research Site
city: Kiew
country: Ukraine
facility: Research Site
Study officials:
affiliation: Rainier Therapeutics
name: Rainier Therapeutics
role: STUDY_CHAIR
References: