Study of Urelumab in Subjects With Advanced and/or Metastatic Malignant Tumors

A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Immunoregulatory Activity of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Malignant Tumors

The purpose of this study is to assess the safety and tolerability of BMS-663513 in subjects with advanced and/or metastatic malignant tumors.

Study Overview

• Status: Completed
• Conditions: Malignant Tumors
• Intervention / Treatment: Drug: Nivolumab; Drug: Urelumab

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 6500017
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects with previously treated advanced malignant solid tumor
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• For certain subjects, willing and able to provide pre-treatment tumor sample

Exclusion Criteria:

• Known or suspected central nervous system metastases or central nervous system as the only source of disease
• Other concomitant malignancies (with some exceptions per protocol)
• Active, known or suspected autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Urelumab (+ Nivolumab) intravenous (IV) infusion	Drug: Nivolumab; Drug: Urelumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of urelumab monotherapy as measured by the dose limiting toxicity (DLT) in subjects with advanced and/or metastatic malignant tumors	From day 1 of treatment up to 60 days of follow-up
Safety of urelumab monotherapy as measured by adverse events (AEs) and serious adverse events (SAEs) in subjects with advanced and/or metastatic malignant tumors	From day 1 of treatment up to 60 days of follow-up
Tolerability of urelumab monotherapy as measured by the DLT in subjects with advanced and/or metastatic malignant tumors	From day 1 of treatment up to 60 days of follow-up
Tolerability of urelumab monotherapy as measured by AEs and SAEs in subjects with advanced and/or metastatic malignant tumors	From day 1 of treatment up to 60 days of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of urelumab-nivolumab combination therapy as measured by AEs and SAEs in subjects with advanced and/or metastatic malignant tumors		From day 1 of treatment up to 100 days of follow-up
Tolerability of urelumab-nivolumab combination therapy as measured by AEs and SAEs in subjects with advanced and/or metastatic malignant tumors		From day 1 of treatment up to 100 days of follow-up
Cmax (Maximum observed serum concentration) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
Ctrough (Trough observed serum concentration) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
Tmax (Time of maximum observed serum concentration) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
AUC(0-T) [Area under the concentration-time curve from time zero to the last quantifiable concentration] of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
AUC(TAU) [Area under the concentration-time curve in one dosing interval] of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
AUC(INF) [Area under the concentration-time curve from time zero to infinity and the extrapolated area] of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
T-HALF (Elimination half life) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
CLT (Total body clearance) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
Vss (Volume of distribution at steady state) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
AI (Accumulation Index: ratio of AUC(TAU) and Cmax in cycle at steady state to those after the first cycle) of urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up
Cmax of urelumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
Coeff of urelumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
Ctrough of urelumab and nivolumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
Tmax of urelumab and nivolumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
AUC(0-T) of urelumab and nivolumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
AUC(TAU) of urelumab and nivolumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
AUC(INF) of urelumab and nivolumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
T-HALF of urelumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
CLT of urelumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
Vss of urelumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up
Anti-drug Antibody (ADA) status of the subject in response to Urelumab when administered alone	21 days/cycle for Urelumab monotherapy	Cycle 1, 2, 4, 8, 12, 16, up to 60 days of follow up
ADA status of the subject in response to Urelumab and Nivolumab when co-administered	28 days/cycle for combination therapy of Urelumab and Nivolumab	Cycle 1, 2, 4, 5, 9, up to 100 days of follow up
Best overall response (BOR) of urelumab monotherapy		Every 6-8 weeks during the treatment period
BOR of urelumab and nivolumab combination therapy		Every 6-8 weeks during the treatment period

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2015
• Primary Completion (Actual): November 11, 2016
• Study Completion (Actual): November 11, 2016

Study Registration Dates

• First Submitted: August 5, 2015
• First Submitted That Met QC Criteria: August 25, 2015
• First Posted (Estimate): August 27, 2015

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Advanced malignant tumors; Metastatic malignant tumors
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA186-110

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes