Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
July 10, 2026 updated by: Bristol-Myers Squibb
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)
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
127
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School of Medicine
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District of Columbia
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Washington D.C., District of Columbia, United States, 20007
- Medstar Georgetown-Lombardi Comprehensive Cancer Center
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New York
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New York, New York, United States, 11065
- Memorial Sloan Kettering Nassau
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- Hillman Cancer Research Pavilion
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
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 |
Other Names:
Other Names:
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|
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 |
Other Names:
Other Names:
|
|
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 |
Other Names:
Other Names:
|
|
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 |
Other Names:
Other Names:
|
|
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 |
Other Names:
Other Names:
|
|
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
|
Other Names:
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|
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
|
Other Names:
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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 |
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of Participants With an Adverse Event (AE)
Time Frame: Up to 3 years
|
incidence of all cause and treatment related adverse events
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Up to 3 years
|
|
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
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Up to 3 years
|
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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
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Up to 3 years
|
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Number of Deaths
Time Frame: Up to 3 years
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incidence of all cause and treatment related deaths
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Up to 3 years
|
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Number of Participants With Select AEs
Time Frame: Up to 3 years
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incidence of all cause and treatment related Adverse events in certain organ systems
|
Up to 3 years
|
|
Laboratory Abnormalities: Specific Liver Tests
Time Frame: Up to 3 years
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Number of Participants with On-Treatment Laboratory Abnormalities in Specific Liver Tests Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
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Up to 3 years
|
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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)
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Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
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Up to 3 years
|
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Time to Response
Time Frame: Up to 3 Years
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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
|
Up to 3 Years
|
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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.
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from the first documented response (irCR or irPR) until progression or death
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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.
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156 weeks
|
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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.
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Up to 3 years
|
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Peak and Trough Concentrations
Time Frame: Up to 64 Weeks
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The peak and trough concentrations of BMS-936558 (MDX-1106) and ipilimumab in participants with quantifiable data
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Up to 64 Weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Callahan MK, Kluger H, Postow MA, Segal NH, Lesokhin A, Atkins MB, Kirkwood JM, Krishnan S, Bhore R, Horak C, Wolchok JD, Sznol M. Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. J Clin Oncol. 2018 Feb 1;36(4):391-398. doi: 10.1200/JCO.2017.72.2850. Epub 2017 Oct 17.
- Nguyen AT, Elia M, Materin MA, Sznol M, Chow J. Cyclosporine for Dry Eye Associated With Nivolumab: A Case Progressing to Corneal Perforation. Cornea. 2016 Mar;35(3):399-401. doi: 10.1097/ICO.0000000000000724.
- Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 14, 2009
Primary Completion (Actual)
February 4, 2014
Study Completion (Actual)
April 1, 2019
Study Registration Dates
First Submitted
December 1, 2009
First Submitted That Met QC Criteria
December 1, 2009
First Posted (Estimated)
December 2, 2009
Study Record Updates
Last Update Posted (Actual)
August 3, 2026
Last Update Submitted That Met QC Criteria
July 10, 2026
Last Verified
March 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Neoplasms by Histologic Type
- Skin Diseases
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Skin Neoplasms
- Skin and Connective Tissue Diseases
- Melanoma
- Amino Acids, Peptides, and Proteins
- Proteins
- Antibodies, Monoclonal, Humanized
- Antibodies, Monoclonal
- Antibodies
- Immunoglobulins
- Immunoproteins
- Blood Proteins
- Serum Globulins
- Globulins
- Nivolumab
- Ipilimumab
Other Study ID Numbers
- CA209-004
- (MDX1106-04) (Other Identifier: Medarex)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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