Overview

This trial is active, not recruiting.

Condition malignant melanoma
Treatments bms-936558 (mdx1106-04), ipilimumab
Phase phase 1
Target CTLA-4
Sponsor Bristol-Myers Squibb
Collaborator Medarex
Start date December 2009
End date January 2017
Trial size 136 participants
Trial identifier NCT01024231, (MDX1106-04), CA209-004

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)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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
bms-936558 (mdx1106-04) Nivolumab
ipilimumab BMS-734016
(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
bms-936558 (mdx1106-04) Nivolumab
ipilimumab BMS-734016
(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
bms-936558 (mdx1106-04) Nivolumab
ipilimumab BMS-734016
(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
bms-936558 (mdx1106-04) Nivolumab
ipilimumab BMS-734016
(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
bms-936558 (mdx1106-04) Nivolumab
ipilimumab BMS-734016
(Experimental)
BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks
bms-936558 (mdx1106-04) Nivolumab
(Experimental)
BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks
bms-936558 (mdx1106-04) Nivolumab
(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
bms-936558 (mdx1106-04) Nivolumab
ipilimumab BMS-734016

Primary Outcomes

Measure
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)

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Bristol-Myers Squibb.