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Safety Study of IL-21/Anti-PD-1 Combination in the Treatment of Solid Tumors

This study is currently recruiting participants.
Verified March 2013 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01629758
First received: June 26, 2012
Last updated: March 28, 2013
Last verified: March 2013
History of Changes
  Purpose

The purpose of this study is to determine whether the combination of the 2 drugs being investigated (IL-21 and anti-PD-1) is safe, and provide preliminary information on the clinical benefits of two different schedules of the combination.


Condition Intervention Phase
Neoplasms by Site
 Biological: BMS-982470
Biological: BMS-936558
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of BMS-982470 (Recombinant Interleukin-21, rIL-21) in Combination With BMS-936558 (Anti-PD-1) in Subjects With Advanced or Metastatic Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety, as measured by the rate of adverse events and serious adverse events [ Time Frame: Approximately up to 4.5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy as measured by tumor assessment (irRECIST and RECIST) [ Time Frame: Week 6 of for the first 4 cycles, Week 6 of alternate cycle starting with cycle 6, End of Treatment (2 years) and approximately every 12 weeks during follow-up (approximately 1 year) ] [ Designated as safety issue: No ]
    Based on immune-related Response Evaluation Criteria for Solid Tumors (irRECIST) 1.1 and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using Best overall response (BOR), Objective response rate (ORR), Duration of Response (DOR), Progression-Free Survival Rate (PFSR),

  • Maximum observed plasma concentration (Cmax) of BMS-982470 and BMS-936558 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Trough observed plasma concentration (Cmin) of BMS-982470 and BMS-936558 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of BMS-982470 and BMS-936558 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-982470 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-982470 and BMS-936558 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of BMS-982470 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Total body clearance (CLT) of BMS-982470 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Volume of distribution at steady-state (Vss) of BMS-982470 and BMS-936558 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Accumulation index; ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (AI) of BMS-982470 and BMS-936558 will be derived from serum concentration versus time data [ Time Frame: Up to 42 timepoints within the first 12 weeks ] [ Designated as safety issue: No ]
  • Immunogenicity as measured by incidence of specific antidrug antibodies (ADA) to BMS-98470 and BMS-936558 [ Time Frame: Up to 2 years + 100 days post-treatment follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: June 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1-Arm A: BMS-982470 (weekly x 4) + BMS-936558
Dose Escalation BMS-982470 10, 30, 50, 75 or 100 µg/kg Solution, Intravenous, During each 6 week cycle: weekly x 4 (i.e during weeks 1 through 4), Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years
 Biological: BMS-982470
Other Name: rIL-21(recombinant interleukin 21)
Biological: BMS-936558
Other Names:
  • Anti-PD-1 (Anti-Programmed-Death-1)
  • MDX-1106
Experimental: Part 1-Arm B: BMS-982470 (3 times/week)) + BMS-936558
Dose Escalation BMS-982470 10, 30, 50, 75 or 100 µg/kg Solution, Intravenous, During each 6 week cycle: 3 times/week during weeks 1 and 3, Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years
 Biological: BMS-982470
Other Name: rIL-21(recombinant interleukin 21)
Biological: BMS-936558
Other Names:
  • Anti-PD-1 (Anti-Programmed-Death-1)
  • MDX-1106
Experimental: Part 2-Arm A: BMS-982470 (weekly x 4) + BMS-936558
Cohort Expansion BMS-982470 (dose selected in Part 1) Solution, Intravenous, During each 6 week cycle: weekly x 4 (i.e during weeks 1 through 4), Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years
 Biological: BMS-982470
Other Name: rIL-21(recombinant interleukin 21)
Biological: BMS-936558
Other Names:
  • Anti-PD-1 (Anti-Programmed-Death-1)
  • MDX-1106
Experimental: Part 2-Arm B: BMS-982470 (3 times/week) + BMS-936558
Cohort Expansion BMS-982470 (dose selected in Part 1) Solution, Intravenous, During each 6 week cycle: 3 times/week during weeks 1 and 3, Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years
 Biological: BMS-982470
Other Name: rIL-21(recombinant interleukin 21)
Biological: BMS-936558
Other Names:
  • Anti-PD-1 (Anti-Programmed-Death-1)
  • MDX-1106

Detailed Description:

Allocation: Part 1 Dose Escalation: Nonrandomized Trial; Part 2 Cohort Expansion: Randomized Trial

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All subjects will have locally advanced or metastatic cancer resistant to standard treatment, for which no additional standard treatment is available, or for which the subject declines standard treatment, excluding cancer in the blood; in Part 2 (Cohort Expansion), tumor types will be further restricted to clear cell renal cell carcinoma or non-small cell lung cancer
  • At least 1 non-irradiated lesion with measurable disease at baseline
  • Availability of an existing tumor biopsy sample (or consent to allow pre-treatment tumor biopsy if sample not available)

Exclusion Criteria:

  • Uncontrolled brain metastases
  • Certain prior drug treatments for the cancer
  • Autoimmune disease
  • Inadequate liver or kidney function
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01629758

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
United States, Arizona
Oncology Research Associates, Pllc D/B/A Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Michael S Gordon, Site 0003            
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Scott Antonia, Site 0001     813-979-6949        
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Charles Drake, Site 0004            
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Laura Chow, Site 0002     206-288-1382        
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trial Information  This link exits the ClinicalTrials.gov site
BMS clinical trial educational resource  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01629758     History of Changes
Other Study ID Numbers: CA220-008
Study First Received: June 26, 2012
Last Updated: March 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on May 23, 2013