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
Last Update Posted : June 17, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Malignant Melanoma | Drug: BMS-936558 (MDX1106-04) Drug: Ipilimumab | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 136 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | December 14, 2009 |
Actual Primary Completion Date : | February 4, 2014 |
Actual Study Completion Date : | April 1, 2019 |

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 |
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab Drug: Ipilimumab Other Name: BMS-734016 |
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 |
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab Drug: Ipilimumab Other Name: BMS-734016 |
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 |
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab Drug: Ipilimumab Other Name: BMS-734016 |
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 |
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab Drug: Ipilimumab Other Name: BMS-734016 |
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 |
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab Drug: Ipilimumab Other Name: BMS-734016 |
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
|
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab |
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
|
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab |
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 |
Drug: BMS-936558 (MDX1106-04)
Other Name: Nivolumab Drug: Ipilimumab Other Name: BMS-734016 |
- 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)
- 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 ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01024231
United States, Connecticut | |
Yale University School Of Medicine | |
New Haven, Connecticut, United States, 06520 | |
United States, District of Columbia | |
Medstar Georgetown-Lombardi Comprehensive Cancer Center | |
Washington, District of Columbia, United States, 20007 | |
United States, New York | |
Memorial Sloan Kettering Nassau | |
New York, New York, United States, 11065 | |
United States, Pennsylvania | |
Hillman Cancer Research Pavilion | |
Pittsburgh, Pennsylvania, United States, 15232 |
Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Bristol-Myers Squibb |
ClinicalTrials.gov Identifier: | NCT01024231 |
Other Study ID Numbers: |
CA209-004 (MDX1106-04) ( Other Identifier: Medarex ) |
First Posted: | December 2, 2009 Key Record Dates |
Last Update Posted: | June 17, 2020 |
Last Verified: | June 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Nerve Tissue Nevi and Melanomas Nivolumab Ipilimumab Antineoplastic Agents, Immunological Antineoplastic Agents |