Malignant MelanomaPhase 1NCT01024231
Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
A Phase 1 study testing BMS-936558 (MDX1106-04) and Ipilimumab in people with Malignant Melanoma, run by Bristol-Myers Squibb at 4 sites in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- BMS-936558 (MDX1106-04) and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 4 sitesUnited States
- Study dates
- 14 Dec 2009to 1 Apr 2019
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Yale University School Of Medicine
New Haven, Connecticut, 06520
Memorial Sloan Kettering Nassau
New York, New York, 11065
Hillman Cancer Research Pavilion
Pittsburgh, Pennsylvania, 15232
Medstar Georgetown-Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
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
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)
- Conditions
- Malignant Melanoma
- Being tested
- BMS-936558 (MDX1106-04), Ipilimumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-936558 (MDX1106-04)Drug
Also called Nivolumab
IpilimumabDrug
Also called BMS-734016
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: BMS-936558 (0.3 mg/kg)+Ipilimumab (3 mg/kg) | Experimental | 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 Receives: Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab |
| Cohort 2: BMS-936558 (1 mg/kg)+Ipilimumab (3 mg/kg) | Experimental | 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 Receives: Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab |
| Cohort 3: BMS-936558 (3 mg/kg)+Ipilimumab (3 mg/kg) | Experimental | 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 Receives: Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab |
| Cohort 4: BMS-936558 (10 mg/kg)+Ipilimumab (3 mg/kg) | Experimental | 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 Receives: Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab |
| Cohort 5: BMS-936558 (10 mg/kg)+Ipilimumab (10 mg/kg) | Experimental | 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 Receives: Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab |
| Cohort 6: BMS-936558 (1 mg/kg) | Experimental | BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks Receives: Drug: BMS-936558 (MDX1106-04) |
| Cohort 7: BMS-936558 (3 mg/kg) | Experimental | BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks Receives: Drug: BMS-936558 (MDX1106-04) |
| Cohort 8: Nivolumab+Ipilimumab | Experimental | 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 Receives: Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With an Adverse Event (AE)
incidence of all cause and treatment related adverse events
Measured: Up to 3 years
Number of Participants With a Serious Adverse Event (AE)
incidence of all cause and treatment related serious adverse events
Measured: Up to 3 years
Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation
incidence of all cause and treatment related adverse events which lead to discontinuation
Measured: Up to 3 years
Number of Deaths
incidence of all cause and treatment related deaths
Measured: Up to 3 years
Number of Participants With Select AEs
incidence of all cause and treatment related Adverse events in certain organ systems
Measured: Up to 3 years
Laboratory Abnormalities: Specific Liver Tests
Number of Participants with On-Treatment Laboratory Abnormalities in Specific Liver Tests Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
Measured: Up to 3 years
Laboratory Abnormalities: Specific Thyroid Tests
Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Measured: Up to 3 years
Secondary outcomes (6)
Objective Response Rate
the total number of participants whose best overall response (BOR) is either irCR or irPR divided by the total number of response-evaluable participants.
Measured: Up to 3 years
Time to Response
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
Measured: Up to 3 Years
Duration of Response
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.
Measured: from the first documented response (irCR or irPR) until progression or death
Progression Free Survival
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.
Measured: 156 weeks
Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi)
Serum samples will be collected to evaluate the development of antibodies to BMS-936558 and to ipilimumab.
Measured: Up to 3 years
Peak and Trough Concentrations
The peak and trough concentrations of BMS-936558 (MDX-1106) and ipilimumab in participants with quantifiable data
Measured: Up to 64 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2009 (estimated)
- Study start14 Dec 2009
- Primary completion4 Feb 2014
- Study completion1 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medarex, Ono Pharma USA Inc
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01024231
- Sponsor's protocol ID
- CA209-004
- Other IDs
- (MDX1106-04)
- Status last verified
- Mar 2021
- First submitted
- 1 Dec 2009
- Last updated
- 3 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 39504507Callahan 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.
PubMed 29040030Nguyen 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.
PubMed 26771550Wolchok 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.
PubMed 23724867