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Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma

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ClinicalTrials.gov Identifier: NCT01024231
Recruitment Status : Active, not recruiting
First Posted : December 2, 2009
Last Update Posted : December 13, 2017
Sponsor:
Collaborators:
Medarex
Ono Pharma USA Inc
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE December 1, 2009
First Posted Date  ICMJE December 2, 2009
Last Update Posted Date December 13, 2017
Actual Study Start Date  ICMJE December 14, 2009
Estimated Primary Completion Date April 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2012)
Safety assessments will be based on adverse event reports and the results of clinical laboratory tests, immune safety tests, physical examinations, vital sign measurements, ECOG performance status, and ECG evaluations [ Time Frame: Up to 12 weeks after the last dose of the last study drug dose (approximately up to 5.5 years) ]
Eastern Cooperative Oncology Group (ECOG), electrocardiogram (ECG)
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
Maximum tolerated dose [ Time Frame: Completion of each dosing cohort ]
Change History Complete list of historical versions of study NCT01024231 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2012)
  • Pharmacokinetic peak and trough concentration of each study drug when given in combination together or in a sequenced regimen [ Time Frame: Cohorts 1-5: Day 1, 2, 3, 8, 15, 22, 43, 64, 85, 106, 127, 148, 169, 253 & 6 & 12 weeks after last dose of study drug. Cohort 6-7: Day 1, 57, 113, 225, 337, 449, 561 & 6 & 12 weeks after last dose of study drug ]
  • Blood samples to test immunogenicity [ Time Frame: Cohorts 1-5: Pre-dose at weeks 0, 6, 12, 21, 24, 36, 60, 84, 108, and 12 weeks after last dose of study drug. Cohorts 6-7: Pre-dose at weeks 1, 9, 18, 36, 54, 72, 90, 108, 126, 144, 162, 180, and 12 weeks after last dose of study drug ]
  • Tumor response evaluations [ Time Frame: Cohorts 1-5: At weeks 12, 18, 24, 30, 36, 48, 60, 72, 84, 96 and 108. Cohorts 6-7: At weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 108, 120, 132, 144, 156, 168, 180 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
  • Safety assessment based on Adverse Event reports, results of clinical laboratory tests, immune safety tests, physical exam, vital signs, ECG evaluation and ECOG [ Time Frame: Safety is assessed at all study timepoints ]
  • Tumor response evaluations [ Time Frame: Tumor response is assessed at weeks 12, 18, 24, 30, 36, 48, 60, 72, 84, 96 and 108 ]
  • Pharmacokinetic peak and trough concentration of each study drug when given in combination compared to historical monotherapy data [ Time Frame: PK is collected pre and post dose ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
Official Title  ICMJE A Phase 1b, Open-label, Multicenter, Multidose, Dose-escalation Study of BMS-936558 (MDX-1106) in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
Brief Summary The purpose of this study is to determine the safety and tolerability of treatment with BMS-936558 (MDX-1106) in combination with Ipilimumab (BMS-734016) when given at the same time or as a sequenced regimen in subjects with unresectable Stage III or Stage IV malignant melanoma (MEL)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Melanoma
Intervention  ICMJE
  • Drug: BMS-936558 (MDX1106-04)
    Other Name: Nivolumab
  • Drug: Ipilimumab
    Other Name: BMS-734016
Study Arms
  • Experimental: Cohort 1: BMS-936558 (0.3 mg/kg)+Ipilimumab (3 mg/kg)

    BMS-936558 (MDX1106-04) 0.3 mg/kg solution, 60 minutes intravenous infusion every 3 (q3) weeks for 21 weeks in induction and every 12 (q12) weeks for 84 weeks in maintenance

    Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance

    Interventions:
    • Drug: BMS-936558 (MDX1106-04)
    • Drug: Ipilimumab
  • Experimental: Cohort 2: BMS-936558 (1 mg/kg)+Ipilimumab (3 mg/kg)

    Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance

    BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance

    Interventions:
    • Drug: BMS-936558 (MDX1106-04)
    • Drug: Ipilimumab
  • Experimental: Cohort 3: BMS-936558 (3 mg/kg)+Ipilimumab (3 mg/kg)

    Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance

    BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance

    Interventions:
    • Drug: BMS-936558 (MDX1106-04)
    • Drug: Ipilimumab
  • Experimental: Cohort 4: BMS-936558 (10 mg/kg)+Ipilimumab (3 mg/kg)

    BMS-936558 (MDX1106-04) 10 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance

    Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance

    Interventions:
    • Drug: BMS-936558 (MDX1106-04)
    • Drug: Ipilimumab
  • Experimental: Cohort 5: BMS-936558 (10 mg/kg)+Ipilimumab (10 mg/kg)

    BMS-936558 (MDX1106-04) 10 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance

    Ipilimumab (BMS-734016) 10 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance

    Interventions:
    • Drug: BMS-936558 (MDX1106-04)
    • Drug: Ipilimumab
  • Experimental: Cohort 6: BMS-936558 (1 mg/kg)
    BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks
    Intervention: Drug: BMS-936558 (MDX1106-04)
  • Experimental: Cohort 7: BMS-936558 (3 mg/kg)
    BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks
    Intervention: Drug: BMS-936558 (MDX1106-04)
  • Experimental: Cohort 8: Nivolumab+Ipilimumab

    Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg solution intravenously q3 weeks, 4 doses for 12 weeks

    Followed by Nivolumab 3 mg/kg solution alone intravenously q2 weeks, 48 doses for a maximum of 96 weeks

    Interventions:
    • Drug: BMS-936558 (MDX1106-04)
    • Drug: Ipilimumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 19, 2013)
136
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2009)
50
Estimated Study Completion Date December 30, 2019
Estimated Primary Completion Date April 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Inclusion Criteria:

  • Histologic diagnosis of malignant melanoma (MEL)
  • Measurable unresectable Stage III or IV MEL
  • ECOG performance status score of 0 or 1
  • Life expectancy ≥4 months
  • For those enrolled in amendment 5 and later, tumor tissue (archival or recent acquisition) must be available
  • For Cohorts 1-5, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma not including any post-incisional adjuvant therapy. Subjects may be treatment naïve. All metastatic melanoma regardless of primary site of disease will be allowed
  • For Cohorts 6-7, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma; this does not include any post-incisional adjuvant therapy. Specifically, subjects must have received ≥3 doses of Ipilimumab therapy and the last dose having been administered within 4-12 weeks of initiation of study treatment

Exclusion Criteria:

  • History of severe hypersensitivity reactions to other mAbs
  • Prior malignancy active within the previous 2 years except for localized cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence
  • Active autoimmune disease or a history of known or suspected autoimmune disease
  • History of recently active diverticulitis or symptomatic peptic ulcer disease and history of adrenal insufficiency
  • Regular narcotic analgesia
  • Active, untreated central nervous system metastasis
  • For subjects enrolled in Cohorts 1-5, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody
  • For subjects enrolled in Cohorts 6-7, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD137 antibodies
  • Any non-oncology vaccine therapy used for prevention of infectious disease
  • Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs
  • Positive tests for human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), hepatitis B, hepatitis C
  • Subjects weighing ≥125 kg are excluded from Cohort 5
  • Subjects in Cohorts 6 and 7 must have received Ipilimumab monotherapy immediately prior to study entry, but must not have received that Ipilimumab as part of a clinical trial
  • Subjects with ocular melanoma are excluded from Cohort 8
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01024231
Other Study ID Numbers  ICMJE CA209-004
(MDX1106-04) ( Other Identifier: Medarex )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE
  • Medarex
  • Ono Pharma USA Inc
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP