Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: BMS-936558 (MDX1106-04); Ipilimumab
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 127.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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)
    

Eligibility criteria:

        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