PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma

NCT ID: NCT01621490

Last Updated: 2024-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-27
• Study Completion Date: 2018-10-25

Brief Summary

The purpose of this study is to evaluate pharmacodynamic changes of Nivolumab and Nivolumab in combination with Ipilimumab treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced)

Detailed Description

Allocation:

Part 1 and 2: Single Arm study

Part 3 and 4: Randomized Controlled Trial

Intervention Model:

Part 1 and 2: Single group: Single arm study

Part 3 and 4: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

Minimum Age:

Part 1: 18

Part 2, 3 and 4: 16

Conditions

Advanced Melanoma; Metastatic Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Part 1-Cohort 1 and 2: Nivolumab

Nivolumab 3 mg/kg solution intravenously Every 2 weeks, Up to 2 years depending on response

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Part 2-Arm A: Nivolumab + Ipilimumab

Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Ipilimumab

Intervention Type: DRUG

Part 3-Arm A: Nivolumab + Ipilimumab

Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Ipilimumab

Intervention Type: DRUG

Part 3-Arm B: Nivolumab

Nivolumab 3 mg/kg solution intravenously as specified

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Part 4-Arm D: Nivolumab + Ipilimumab

Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Ipilimumab

Intervention Type: DRUG

Part 4-Arm E: Nivolumab

Nivolumab 3 mg/kg solution intravenously as specified

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Interventions

Nivolumab

Intervention Type: BIOLOGICAL

Ipilimumab

Intervention Type: DRUG

Other Intervention Names

BMS-936558 (MDX1106); BMS734016; Yervoy

Eligibility Criteria

Inclusion Criteria

• Men and women >18 years
• Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
• Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
• Subject must have histologic or cytologic confirmation of advanced melanoma
• Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies

• Men and women >16 years
• Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
• Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
• Subjects must never received anti-CTLA4 therapy
• Subjects must have histologic or cytologic confirmation of advanced melanoma
• Subjects must have at least two measurable lesions at baseline by CT or MRI as per RECIST 1.1 criteria
• Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
• Subjects in Part 4 must have brain metastases

Exclusion Criteria

• Active or progressing brain metastases
• Other concomitant malignancies (with some exceptions per protocol)
• Active or history of autoimmune disease
• Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
• History of any hepatitis
• Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy

Part 2, 3 and 4:

• Active or progressing brain metastases (except for Part 4 subjects)
• Other concomitant malignancies (with some exceptions per protocol)
• Active or history of autoimmune disease
• Positive test for HIV 1&2 or known AIDS
• History of any hepatitis
• Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies

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

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Ucla

Los Angeles, California, United States

University Of Chicago

Chicago, Illinois, United States

Sidney kimmel comprehensive cancer center at johns hopkins

Lutherville, Maryland, United States

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Providence Portland Medical Center

Portland, Oregon, United States

Vanderbilt-Ingram Cancer Ctr

Nashville, Tennessee, United States

The University Of Texas MD Anderson Cancer Center

Houston, Texas, United States

University Of Virginia

Charlottesville, Virginia, United States

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Local Institution - 0016

Amsterdam, , Netherlands

Local Institution - 0008

Pamplona, , Spain

Countries

United States; Netherlands; Spain

References

Kim YJ, Sheu KM, Tsoi J, Abril-Rodriguez G, Medina E, Grasso CS, Torrejon DY, Champhekar AS, Litchfield K, Swanton C, Speiser DE, Scumpia PO, Hoffmann A, Graeber TG, Puig-Saus C, Ribas A. Melanoma dedifferentiation induced by IFN-gamma epigenetic remodeling in response to anti-PD-1 therapy. J Clin Invest. 2021 Jun 15;131(12):e145859. doi: 10.1172/JCI145859.

Reference Type: DERIVED

PMID: 33914706 (View on PubMed)

Anagnostou V, Bruhm DC, Niknafs N, White JR, Shao XM, Sidhom JW, Stein J, Tsai HL, Wang H, Belcaid Z, Murray J, Balan A, Ferreira L, Ross-Macdonald P, Wind-Rotolo M, Baras AS, Taube J, Karchin R, Scharpf RB, Grasso C, Ribas A, Pardoll DM, Topalian SL, Velculescu VE. Integrative Tumor and Immune Cell Multi-omic Analyses Predict Response to Immune Checkpoint Blockade in Melanoma. Cell Rep Med. 2020 Nov 17;1(8):100139. doi: 10.1016/j.xcrm.2020.100139. eCollection 2020 Nov 17.

Reference Type: DERIVED

PMID: 33294860 (View on PubMed)

Stein JE, Soni A, Danilova L, Cottrell TR, Gajewski TF, Hodi FS, Bhatia S, Urba WJ, Sharfman WH, Wind-Rotolo M, Edwards R, Lipson EJ, Taube JM. Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response. Ann Oncol. 2019 Apr 1;30(4):589-596. doi: 10.1093/annonc/mdz019.

Reference Type: DERIVED

PMID: 30689736 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

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

2012-001840-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-038

Identifier Type: -

Identifier Source: org_study_id