Ph 1B B-701 in Combination With Pembrolizumab in Metastatic Transitional Cell Carcinoma of the Urothelial Tract

NCT02925533 | Terminated Phase 1 DMC

• 1 other identifier: 16-246
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of two experimental drugs as a possible treatment for Bladder Cancer that recurred after treatment with standard therapy, or Bladder Cancer that got worse while on treatment with standard therapy. The following interventions will be involved in this study:

• B-701
• Pembrolizumab

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Urothelial Cancer

Outcome Measures

Primary Outcomes (1)

• Preliminarily Evaluate The Safety Of B-701 In Combination With Pembrolizumab For The Treatment Of TCC

  Safety will be assessed through summaries of AEs (adverse events), changes in laboratory test results, ECGs (electrocardiograms), and changes in vital signs

  2 years

Secondary Outcomes (1)

• To Assess The Efficacy Of B-701 In Combination With Pembrolizumab For The Treatment Of TCC

  2 years

Study Arms (1)

B-701 and Pembrolizumab

EXPERIMENTAL

* B-701 will be administered every 3 weeks intravenously * Pembrolizumab will be administered every 3 weeks intravenously

Drug: B-701; Drug: Pembrolizumab

Interventions

B-701 DRUG

B-701 is a phage-derived, affinity-matured, human monoclonal antibody (mAb) specific for FGFR3. It is based on a human immunoglobulin G1 (IgG1) framework containing heavy chain VHIII and light chain VκI subgroup sequences.

B-701 and Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is an mAb that binds to the programmed cell death protein 1 (PD-1) receptor and blocks its interaction with programmed death-ligand 1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

Also known as: Keytruda, MK-3475

B-701 and Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must have Stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or transitional cell carcinoma (TCC) arising in another location of the urinary tract, including urethra, ureter, and renal pelvis. The diagnosis must be histologically or cytologically confirmed. Mixed histologies are permitted as long as TCC is the major component (i.e. \> 50% of the pathologic specimen). Pure or predominant squamous cell carcinomas or adenocarcinomas are not permitted.
• Relapsed after or refractory to one or two prior lines of chemotherapy for advanced or metastatic/recurrent disease (at least one cycle each) which have not included a PD-L1 or FGFR inhibitor. At least one regimen should have included a platinum agent unless contraindicated for the subject. Prior neoadjuvant or adjuvant chemotherapy (without a PD-L1 or FGFR inhibitor) 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. However, a regimen of neoadjuvant or adjuvant chemotherapy will be counted as first-line chemotherapy if the patient progressed within 12 months of the last dose.
• Age ≥ 18 years
• Eastern cooperative oncology group (ECOG) performance status ≤ 1 (Karnofsky ≥ 60%)
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥ 3000/mcL
• absolute neutrophil count ≥ 1500/mcL
• platelets ≥ 75,000/mcL
• hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• total bilirubin within normal institutional limits
• EXCEPTION: Subjects with known Gilbert's disease: total bilirubin ≤ 3 × institutional upper limit of normal (ULN)
• aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 × institutional ULN
• EXCEPTION: Subjects with documented liver metastases: AST and/or ALT ≤ 5 × institutional ULN
• creatinine within normal institutional limits OR
• creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (derived by the Cockcroft-Gault formula \[Cockcroft 1976\])

You may not qualify if:

• Participants who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• Participants who are receiving, or have received, any other investigational drugs or devices within the 2 weeks prior to the first dose of study medications.
• Participants who received major surgery must be recovered adequately from the toxicity and/or complications from the interventions prior to starting therapy.
• Participants with a diagnosis of immunodeficiency or who are receiving systemic steroid therapy (\>5 mg prednisone or its equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Participants who have a primary central nervous system (CNS) malignancy, or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Individuals with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
• Evaluable or measurable disease outside the CNS
• Radiographic demonstration of stability upon the completion of CNS directed therapy and no evidence of interim progression (for at least 4 weeks prior to the first dose of study drug) between the completion of CNS-directed therapy and the screening radiographic procedure
• The screening CNS radiographic procedure is ≥ 8 weeks since completion of radiotherapy and ≥ 4 weeks since the discontinuation of corticosteroids and anticonvulsants Note: These exceptions do not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Participants with a history of allergic reactions attributed to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• Participants with active autoimmune disease that has required systemic treatment (\>5 mg of prednisone or its equivalent) in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Participants with known evidence of active, non-infectious pneumonitis.
• Participants with an active infection requiring systemic therapy.
• Participants who have received a live vaccine within 30 days of planned start of study therapy.
• Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Participants who have had a prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to Cycle 1 Day 1 or who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier.

Sponsors & Collaborators

• Mark Pomerantz, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Rainier Therapeutics: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

B701 protein, Human herpesvirus 6; pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Mark Pomerantz, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: October 6, 2016
• Study Start: December 14, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 27, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)