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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Medarex
Ono Pharma USA Inc
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01024231
First received: December 1, 2009
Last updated: July 9, 2014
Last verified: April 2014

December 1, 2009
July 9, 2014
December 2009
October 2015   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: Yes ]
Eastern Cooperative Oncology Group (ECOG), electrocardiogram (ECG)
Maximum tolerated dose [ Time Frame: Completion of each dosing cohort ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01024231 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Tumor response evaluations [ Time Frame: Tumor response is assessed at weeks 12, 18, 24, 30, 36, 48, 60, 72, 84, 96 and 108 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
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

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)

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Melanoma
  • Drug: BMS-936558 (MDX1106-04)
    Other Name: Nivolumab
  • Drug: Ipilimumab
    Other Name: BMS-734016
  • 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
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122-33. doi: 10.1056/NEJMoa1302369. Epub 2013 Jun 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
136
October 2015
October 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01024231
CA209-004, (MDX1106-04)
Yes
Bristol-Myers Squibb
Bristol-Myers Squibb
  • Medarex
  • Ono Pharma USA Inc
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
April 2014

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