Clinical trial NCT02401542: Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
Official title: A Dose Escalation, Expansion Study of Vofatamab (B-701) Alone, Plus Docetaxel, or Versus Docetaxel in Subjects With Locally Advanced or Metastatic Urothelial Cell Carcinoma Who Have Relapsed After, or Are Refractory to Standard Therapy
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
vofatamab
FGFR3
invasive bladder cancer
targeted therapy
Transitional Cell Carcinoma
TCC
Phase 2
second line therapy
monoclonal antibody
docetaxel
combination therapy
Phase 1
monotherapy
B-701
Lead sponsor: Rainier Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-03-30
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2(b), sequential, dose escalation, open-label, randomized expansion, multicenter, efficacy and safety study of vofatamab alone or in combination with docetaxel, or versus docetaxel in FGFR3 mutant/fusion subjects with Stage IV, locally advanced or metastatic UCC who have relapsed after, or are refractory to at least one prior line of chemotherapy. This study is divided into 3 phases: Phase 1b (Cohort 1), Phase 2 (Cohorts 2 and 3), and Phase 2b (Monotherapy Expansion Phase and Randomized Phase).

Detailed description: This is a Phase 1/2(b), sequential, dose escalation, open-label, randomized expansion, multicenter, efficacy and safety study of vofatamab alone or in combination with docetaxel, or versus docetaxel in FGFR3 mutant/fusion subjects with Stage IV, locally advanced or metastatic UCC who have relapsed after, or are refractory to at least one prior line of chemotherapy. Vofatamab is a novel monoclonal antibody specific for fibroblast growth factor receptor 3 (FGFR3) that is being developed to target FGFR3-positive tumors.

This study is divided into 3 phases: Phase 1b (Cohort 1), Phase 2 (Cohorts 2 and 3), and Phase 2b (Monotherapy Expansion Phase and Randomized Phase).

Eligibility criteria: Key Disease Specific Inclusion Criteria:

1. Stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or TCC arising in another location of the urinary tract, including urethra, ureter, and renal pelvis
2. Histological or cytological diagnosis of UCC.
3. Relapsed after or are refractory to at least one prior line of chemotherapy which has not included a taxane (with the exception of Cohort 3 of Phase 2 and Phase 2b Monotherapy Expansion of Phase 2b which will allow the enrollment of patients with prior treatment with a taxane)
4. Subjects must have received at least one prior chemotherapeutic regimen (at least one cycle each) for advanced or metastatic/recurrent disease, of which at least one regimen included a platinum agent (unless contraindicated).
5. Prior neoadjuvant or adjuvant chemotherapy (without a taxane, except Cohort 3 of Phase 2 and Phase 2b Monotherapy Expansion, which will allow the enrollment of subjects with prior treatment with a taxane) is permitted and will not be counted as first-line chemotherapy, as long as the subject has not progressed within 12 months of the last dose.
6. Measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Phase 2 and Phase 2b Specific Inclusion Criteria:

1. Patient must be confirmed to have a FGFR3 genomic alteration at the time of documentation of advanced disease.
2. Relapsed after or are refractory to an immune checkpoint inhibitor. This inclusion criterion does not apply if the checkpoint inhibitor is contraindicated.

Main Exclusion Criteria:

* Prior anti-cancer therapy within 2 weeks prior to Cycle 1, Day 1
* Prior treatment with an inhibitor that is targeted primarily to FGFRs
* Clinically significant comorbid medical conditions or lab abnormalities
* History of major bleeding (requiring a blood transfusion ≥ 2 units) not related to a tumor within the past 12 months
* History of clinically significant coagulation or platelet disorder in the past 12 months
* Currently receiving anticoagulation treatment
* Incomplete healing from wounds from prior surgery
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at screening
* Presence of positive test results for Hepatitis B or Hepatitis C
* Known history of human immunodeficiency virus (HIV) seropositive status

Primary outcomes:
measure: Primary Efficacy Outcome: Progression Free Survival (PFS)
timeFrame: 3-4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Research Site
state: Arizona
city: Goodyear
country: United States
facility: Research Site
state: Arizona
city: Duarte
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Fort Wayne
country: United States
facility: Reaserach Site
state: Indiana
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Syracuse
country: United States
facility: Research Site
state: New York
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Olomouc
country: Czechia
facility: Research Site
city: Prague
country: Czechia
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Modena
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Negrar
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Incheon
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: Seoul
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: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Lugo
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Vigo
country: Spain
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: İstanbul
country: Turkey
facility: Research Site
city: İzmir
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Preston
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Rainier Therapeutics
name: Rainier Therapeutics
role: STUDY_CHAIR
References: