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

Malignant Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01024231
• Other study ID #: CA209-004
• Secondary ID: (MDX1106-04)
• Status: Completed
• Phase: Phase 1
• Start date: December 14, 2009
• Est. completion date: April 1, 2019

Study information

• Verified date: March 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: April 1, 2019
• Est. primary completion date: February 4, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Drug:
• BMS-936558 (MDX1106-04)

• Ipilimumab

Locations

Country	Name	City	State
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	Hillman Cancer Research Pavilion	Pittsburgh	Pennsylvania
United States	Medstar Georgetown-Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Medarex, Ono Pharma USA Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With an Adverse Event (AE)	incidence of all cause and treatment related adverse events	Up to 3 years
Primary	Number of Participants With a Serious Adverse Event (AE)	incidence of all cause and treatment related serious adverse events	Up to 3 years
Primary	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
Primary	Number of Deaths	incidence of all cause and treatment related deaths	Up to 3 years
Primary	Number of Participants With Select AEs	incidence of all cause and treatment related Adverse events in certain organ systems	Up to 3 years
Primary	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
Primary	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	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.	Up to 3 years
Secondary	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	Up to 3 Years
Secondary	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.	from the first documented response (irCR or irPR) until progression or death
Secondary	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.	156 weeks
Secondary	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.	Up to 3 years
Secondary	Peak and Trough Concentrations	The peak and trough concentrations of BMS-936558 (MDX-1106) and ipilimumab in participants with quantifiable data	Up to 64 Weeks

External Links

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