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

NCT ID: NCT01024231

Last Updated: 2021-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-14
• Study Completion Date: 2019-04-01

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

Interventions

BMS-936558 (MDX1106-04)

Intervention Type: DRUG

Ipilimumab

Intervention Type: DRUG

Other Intervention Names

Nivolumab; BMS-734016

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medarex

INDUSTRY

Sponsor Role: collaborator

Ono Pharma USA Inc

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Yale University School Of Medicine

New Haven, Connecticut, United States

Medstar Georgetown-Lombardi Comprehensive Cancer Center

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

Memorial Sloan Kettering Nassau

New York, New York, United States

Hillman Cancer Research Pavilion

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39504507 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29040030 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26771550 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23724867 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

https://www.bms.com/researchers-and-partners/investigator-inquiry-form.html

Investigator Inquiry Form

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

(MDX1106-04)

Identifier Type: OTHER

Identifier Source: secondary_id

CA209-004

Identifier Type: -

Identifier Source: org_study_id