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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Medarex
Ono Pharma USA Inc
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01024231
First received: December 1, 2009
Last updated: July 9, 2014
Last verified: April 2014
  Purpose

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)


Condition Intervention Phase
Malignant Melanoma
Drug: BMS-936558 (MDX1106-04)
Drug: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    Eastern Cooperative Oncology Group (ECOG), electrocardiogram (ECG)


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 136
Study Start Date: December 2009
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01024231

Locations
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Georgetown University Med Ctr
Washington, District of Columbia, United States, 20007
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 11065
United States, Pennsylvania
Hillman Cancer Research Pavilion
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Bristol-Myers Squibb
Medarex
Ono Pharma USA Inc
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01024231     History of Changes
Other Study ID Numbers: CA209-004, (MDX1106-04)
Study First Received: December 1, 2009
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 19, 2014