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

NCT01024231 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: CA209-004(MDX1106-04)
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 4

Brief 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)

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (7)

• Number of Participants With an Adverse Event (AE)

  incidence of all cause and treatment related adverse events

  Up to 3 years

• Number of Participants With a Serious Adverse Event (AE)

  incidence of all cause and treatment related serious adverse events

  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

  Up to 3 years

• Number of Deaths

  incidence of all cause and treatment related deaths

  Up to 3 years

• Number of Participants With Select AEs

  incidence of all cause and treatment related Adverse events in certain organ systems

  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)

  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)

  Up to 3 years

Secondary Outcomes (6)

• Objective Response Rate

  Up to 3 years

• Time to Response

  Up to 3 Years

• Duration of Response

  from the first documented response (irCR or irPR) until progression or death

• Progression Free Survival

  156 weeks

• Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi)

  Up to 3 years

Study Arms (8)

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

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

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

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

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

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

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

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

Drug: BMS-936558 (MDX1106-04); Drug: Ipilimumab

Interventions

BMS-936558 (MDX1106-04) DRUG

Also known as: Nivolumab

Cohort 1: BMS-936558 (0.3 mg/kg)+Ipilimumab (3 mg/kg); Cohort 2: BMS-936558 (1 mg/kg)+Ipilimumab (3 mg/kg); Cohort 3: BMS-936558 (3 mg/kg)+Ipilimumab (3 mg/kg); Cohort 4: BMS-936558 (10 mg/kg)+Ipilimumab (3 mg/kg); Cohort 5: BMS-936558 (10 mg/kg)+Ipilimumab (10 mg/kg); Cohort 6: BMS-936558 (1 mg/kg); Cohort 7: BMS-936558 (3 mg/kg); Cohort 8: Nivolumab+Ipilimumab

Ipilimumab DRUG

Also known as: BMS-734016

Cohort 1: BMS-936558 (0.3 mg/kg)+Ipilimumab (3 mg/kg); Cohort 2: BMS-936558 (1 mg/kg)+Ipilimumab (3 mg/kg); Cohort 3: BMS-936558 (3 mg/kg)+Ipilimumab (3 mg/kg); Cohort 4: BMS-936558 (10 mg/kg)+Ipilimumab (3 mg/kg); Cohort 5: BMS-936558 (10 mg/kg)+Ipilimumab (10 mg/kg); Cohort 8: Nivolumab+Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Medarex: collaborator
• Ono Pharma USA Inc: collaborator

Study Sites (4)

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Medstar Georgetown-Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Memorial Sloan Kettering Nassau

New York, New York, 11065, United States

Location

Hillman Cancer Research Pavilion

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (4)

• 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.

  PMID: 39504507 DERIVED

• 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.

  PMID: 29040030 DERIVED

• 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.

  PMID: 26771550 DERIVED

• 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.

  PMID: 23724867 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 2, 2009
• Study Start: December 14, 2009
• Primary Completion: February 4, 2014
• Study Completion: April 1, 2019
• Last Updated: March 22, 2021
• Results First Posted: March 22, 2021

Record last verified: 2021-03

Locations

US (4)