Clinical Trials/NCT01471210

NCT01471210

Completed

Phase 1

A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Immunoregulatory Activity of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

Bristol-Myers Squibb15 sites in 2 countries124 target enrollmentFebruary 2012

ConditionsCancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma

InterventionsUrelumab (BMS-663513)

DrugsUrelumab (BMS-663513)

Overview

Phase: Phase 1
Intervention: Urelumab (BMS-663513)
Conditions: Cancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma
Sponsor: Bristol-Myers Squibb
Enrollment: 124
Locations: 15
Primary Endpoint: Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of the study is to assess the safety, tolerability, pharmacokinetics and immunoregulatory activity of urelumab (BMS-663513) in cancer subjects with advanced and/or metastatic tumors and relapsed/refractory B-Cell Non-Hodgkin's Lymphoma

Registry

clinicaltrials.gov

Start Date

February 2012

End Date

April 2016

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed Written Informed Consent
•The signed informed consent form
•Target Population
•Subjects with advanced and/or metastatic solid tumors or B-NHL who are either refractory to or have relapsed from standard therapies, or for whom a standard therapy does not exist with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
•Life expectancy of 12 weeks or greater
•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
•Adequate organ and marrow function
•For certain subjects, willing and able to provide pre- and post-treatment fresh tumor biopsies
•Age and Reproductive Status
•Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks prior to initiation of dosing, and for at least 60 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized

Exclusion Criteria

•Target Disease Exceptions
•Subjects with known or suspected brain metastasis unless previously treated and without evidence of progression
•Subjects with a history of prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured
•Subjects with hepatocellular carcinoma
•Medical History and Concurrent Diseases
•Any active autoimmune disease or documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo, psoriasis inactive within past 2 years, resolved childhood asthma/atopy, or thyroid disease controlled by replacement therapy without the need for immunosuppression
•Known or suspected human immunodeficiency virus (HIV) or hepatitis A(acute), B or C infection
•History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug-related, auto-immune)
•Evidence of active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy \< 7 days prior to administration of study medication
•History of clinically significant cardiac disease, including but not limited to a history (personal or family) of congenital long QT syndrome

Arms & Interventions

Part 1 : Urelumab (BMS-663513) Dose escalation

Urelumab (BMS-663513) solution administered intravenously on specified days

Intervention: Urelumab (BMS-663513)

Part 2 : Urelumab (BMS-663513) Cohort Expansion

Urelumab (BMS-663513) solution administered intravenously on specified days

Intervention: Urelumab (BMS-663513)

Part 3:Urelumab (BMS-663513) Tumor-specific Cohort Expansions

Enrollment of subjects of three specific tumor types \[(colorectal cancer (CRC), head and neck squamous cell carcinoma (SCCHN), and B-Cell non-Hodgkin's lymphoma (B-NHL)\] who will be treated at the Maximum Tolerated Dose (MTD) (or highest dose tested)

Intervention: Urelumab (BMS-663513)

Part 4:Urelumab (BMS-663513) Cohort Expansion in B-NHL

Arm A and Arm B: Urelumab (BMS-663513) liquid administered intravenously on specified days exploring q3w and q6w dosing regimen

Intervention: Urelumab (BMS-663513)

Outcomes

Primary Outcomes

Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests

Time Frame: Every 3 weeks from Baseline (Day 1) for up to 2 years

The incidence of adverse events will be tabulated and reviewed for potential significance and clinical Importance.

Dose-limiting toxicity and maximum tolerated dose of Urelumab (BMS-663513) as determined by the incidence of dose-limiting toxicities

Time Frame: Every 3 weeks from Baseline (Day 1) for up to 9 weeks of therapy

Secondary Outcomes

Maximum observed serum concentrations (Cmax) of Urelumab (BMS-663513)(Cycle 1 Day 1)
Minimum observed serum concentrations (Cmin) of Urelumab (BMS-663513)(Cycle 2 Day 1, Cycle 3 Day 1, every 12 weeks thereafter up to 2 years)
Time of maximum observed serum concentration (Tmax) of Urelumab (BMS-663513)(Cycle 1 Day 1)
Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of Urelumab (BMS-663513)(Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years)
Plasma half-life (T-HALF) of Urelumab (BMS-663513)(Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years)
Total body clearance (CLT) of Urelumab (BMS-663513)(Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years)
Volume of distribution at steady-state (Vss) of Urelumab (BMS-663513)(Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years)
Human Anti-human Antibodies(Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years)
Tumor response and progression as determined by proportion of patients with best overall response (BOR), progression-free survival (PFS), objective response rate (ORR), time to response, and duration of response(9 weeks from Baseline (Day 1) and every 9 weeks until disease progression, death or last tumor assessment (Approximately up to 2 years))