Clinical Trial: NCT02401542 - My Cancer Genome

NCT02401542

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. 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).

Related Conditions:

Urothelial Carcinoma

Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02401542

Trial Eligibility

Document

Title

Brief Title: 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

Clinical Trial IDs

ORG STUDY ID: B-701-U21
SECONDARY ID: 2017-001319-36
NCT ID: NCT02401542

Conditions

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

Interventions

Drug	Synonyms	Arms
Vofatamab	B-701, MFGR1877S, R3Mab	Vofatamab
Docetaxel	Docefrez, Taxotere	Placebo plus docetaxel
Placebo		Placebo plus docetaxel

Purpose

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).

Trial Arms

Name	Type	Description	Interventions
Vofatamab plus docetaxel	Active Comparator	IV infusion of docetaxel, 75 mg/m2, followed by IV infusion of vofatamab, 25 mg/kg, on day one of each 21-day cycle. One additional IV infusion of vofatamab (25 mg/kg) given on Day 8 of Cycle 1. Dosing with vofatamab and docetaxel will continue in each patient until disease progression, unacceptable toxicity, death, or study exit, including withdrawal of patient consent or study termination. Docetaxel treatment beyond 12 cycles of therapy may be considered at the discretion of the treating investigator and Medical Monitor.	Vofatamab Docetaxel
Placebo plus docetaxel	Placebo Comparator	IV infusion of docetaxel, 75 mg/m2, followed by IV infusion of placebo on day one of each 21-day cycle. One additional IV infusion of placebo given on Day 8 of Cycle 1. Dosing of docetaxel and placebo will continue in each patient until disease progression, unacceptable toxicity, death, or study exit, including withdrawal of patient consent or study termination. Docetaxel treatment beyond 12 cycles of therapy may be considered at the discretion of the treating investigator and Medical Monitor	Docetaxel Placebo
Vofatamab	Experimental	IV infusion vofatamab, 25 mg/kg on day one each 21-day cycle. One additional IV infusion of vofatamab (25 mg/kg) given on Day 8 of Cycle 1. Dosing of vofatamab will continue in each patient until disease progression, unacceptable toxicity, death, or study exit, including withdrawal of patient consent or study termination.	Vofatamab

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

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

Primary Outcome Measures

Measure:	Primary Efficacy Outcome: Progression Free Survival (PFS)
Time Frame:	3-4 years
Safety Issue:
Description:	Efficacy of vofatamab plus docetaxel, compared with docetaxel plus placebo, and vofatamab alone as measured by PFS; measured from randomization to first occurrence of disease progression (per RECIST v1.1) or death, whichever occurs first. A patient has had to receive at least one vofatamab dose. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Details

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

Trial 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

Last Updated

March 9, 2020

Clinical Trials /

Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma