Clinical trial NCT01024231: Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Medarex
name: Ono Pharma USA Inc
First posted: 2009-12-02
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Up to 3 years
measure: Number of Participants With a Serious Adverse Event (AE)
timeFrame: Up to 3 years
measure: Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation
timeFrame: Up to 3 years
measure: Number of Deaths
timeFrame: Up to 3 years
measure: Number of Participants With Select AEs
timeFrame: Up to 3 years
measure: Laboratory Abnormalities: Specific Liver Tests
timeFrame: Up to 3 years
measure: Laboratory Abnormalities: Specific Thyroid Tests
timeFrame: Up to 3 years
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Up to 3 years
measure: Time to Response
timeFrame: Up to 3 Years
measure: Duration of Response
timeFrame: from the first documented response (irCR or irPR) until progression or death
measure: Progression Free Survival
timeFrame: 156 weeks
measure: Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi)
timeFrame: Up to 3 years
measure: Peak and Trough Concentrations
timeFrame: Up to 64 Weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Washington
country: United States
facility: Medstar Georgetown-Lombardi Comprehensive Cancer Center
state: District of Columbia
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Pittsburgh
country: United States
facility: Hillman Cancer Research Pavilion
state: Pennsylvania
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.