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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 : Completed
First Posted : December 2, 2009
Results First Posted : March 22, 2021
Last Update Posted : March 22, 2021
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
Results First Submitted Date  ICMJE August 28, 2020
Results First Posted Date  ICMJE March 22, 2021
Last Update Posted Date March 22, 2021
Actual Study Start Date  ICMJE December 14, 2009
Actual Primary Completion Date February 4, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2021)
  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 3 years ]
    incidence of all cause and treatment related adverse events
  • Number of Participants With a Serious Adverse Event (AE) [ Time Frame: Up to 3 years ]
    incidence of all cause and treatment related serious adverse events
  • Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation [ Time Frame: Up to 3 years ]
    incidence of all cause and treatment related adverse events which lead to discontinuation
  • Number of Deaths [ Time Frame: Up to 3 years ]
    incidence of all cause and treatment related deaths
  • Number of Participants With Select AEs [ Time Frame: Up to 3 years ]
    incidence of all cause and treatment related Adverse events in certain organ systems
  • Laboratory Abnormalities: Specific Liver Tests [ Time Frame: Up to 3 years ]
    Number of Participants with On-Treatment Laboratory Abnormalities in Specific Liver Tests Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
  • Laboratory Abnormalities: Specific Thyroid Tests [ Time Frame: Up to 3 years ]
    Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
Maximum tolerated dose [ Time Frame: Completion of each dosing cohort ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2021)
  • Objective Response Rate [ Time Frame: Up to 3 years ]
    the total number of participants whose best overall response (BOR) is either irCR or irPR divided by the total number of response-evaluable participants.
  • Time to Response [ Time Frame: Up to 3 Years ]
    the time from the first dose of study drug until the first documentation of irCR or irPR, as related to current database lock date or most current tumor measurement
  • Duration of Response [ Time Frame: from the first documented response (irCR or irPR) until progression or death ]
    the time from the first documented response (irCR or irPR) until progression or death, whichever occurs first. For participants who did not progress or die, duration of response will be censored on the date of the last tumor assessment.
  • Progression Free Survival [ Time Frame: 156 weeks ]
    the time from the first dose to the first observation of disease progression or death due to any cause. If a participant has not progressed or died at the time of analysis, PFS will be censored on the date of the last disease assessment. Participants who did not have any on-study tumor assessments and did not die will be censored on the date of the first dose of study medication.
  • Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi) [ Time Frame: Up to 3 years ]
    Serum samples will be collected to evaluate the development of antibodies to BMS-936558 and to ipilimumab.
  • Peak and Trough Concentrations [ Time Frame: Up to 64 Weeks ]
    The peak and trough concentrations of BMS-936558 (MDX-1106) and ipilimumab in participants with quantifiable data
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 Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures 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  ICMJE 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  ICMJE
  • 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 Completed
Actual Enrollment  ICMJE
 (submitted: March 19, 2021)
127
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2009)
50
Actual Study Completion Date  ICMJE April 1, 2019
Actual Primary Completion Date February 4, 2014   (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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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  ICMJE 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 March 2021

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