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

NCT01621490 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA209-0382012-001840-23
• Study Type: interventional
• Target: 170
• Locations: 3 countries
• Sites: 14

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)

Conditions

Advanced Melanoma; Metastatic Melanoma

Outcome Measures

Primary Outcomes (2)

• Median Change From Baseline to Week 7, of Interferon (IFN) and Interferon Gamma (IFN-gamma) Inducible Factors

  Baseline and post-treatment modulation of serum levels of chemokines, cytokines and other immune mediators were assessed by techniques that included ELISA or other multiplex-based assay methods. Primary analysis included IFN-gamma and IFN-gamma inducible factors, including chemokine \[C-X-C motif\] ligand 9 (CXCL9) and CXCL10

  From last non-missing value prior to first dose to week 7 day 1

• Tumor Infiltrating Lymphocytes (TILs) as Measured by Medians in Percent Positive CD8 and Positive CD4 at Baseline and On-treatment Biopsy, Both Using the Mosaic Singleplex IHC Assay

  Biomarkers examined were percent positive CD8 and percent positive CD4, both using the Mosaic Singleplex IHC assay. Analyses are presented with the medians at baseline and on-treatment, rather than the median change because the baseline values differed across groups. Baseline was defined as the last non-missing value on or prior to the first dose of study therapy. Biopsies were also collected on treatment.

  From last non-missing value prior to first dose to week 4 day 1

Secondary Outcomes (14)

• Frequency of Adverse Events or Death

  Includes events reported between first dose and up to 100 days after last dose of study medication (up to approximately 73 months).

• Frequency of AEs Leading to Discontinuation of Study Drug and SAEs

  From enrollment to 100 days after the last dose date (up to approximately 73 months)

• Number of Laboratory Abnormalities in Specific Liver Tests

  101-120 days after last dose.

• Number of Laboratory Abnormalities in Specific Thyroid Tests

  101-120 days after last dose.

• Objective Response Rate (ORR)

  Approximately every 8 weeks until disease progression and in follow-up if no progression (up to approximately 73 months)

Study Arms (6)

Part 1-Cohort 1 and 2: Nivolumab

EXPERIMENTAL

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

Biological: Nivolumab

Part 2-Arm A: Nivolumab + Ipilimumab

EXPERIMENTAL

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

Biological: Nivolumab; Drug: Ipilimumab

Part 3-Arm A: Nivolumab + Ipilimumab

EXPERIMENTAL

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

Biological: Nivolumab; Drug: Ipilimumab

Part 3-Arm B: Nivolumab

EXPERIMENTAL

Nivolumab 3 mg/kg solution intravenously as specified

Biological: Nivolumab

Part 4-Arm D: Nivolumab + Ipilimumab

EXPERIMENTAL

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

Biological: Nivolumab; Drug: Ipilimumab

Part 4-Arm E: Nivolumab

EXPERIMENTAL

Nivolumab 3 mg/kg solution intravenously as specified

Biological: Nivolumab

Interventions

Nivolumab BIOLOGICAL

Also known as: BMS-936558 (MDX1106)

Part 1-Cohort 1 and 2: Nivolumab; Part 2-Arm A: Nivolumab + Ipilimumab; Part 3-Arm A: Nivolumab + Ipilimumab; Part 3-Arm B: Nivolumab; Part 4-Arm D: Nivolumab + Ipilimumab; Part 4-Arm E: Nivolumab

Ipilimumab DRUG

Also known as: BMS734016, Yervoy

Part 2-Arm A: Nivolumab + Ipilimumab; Part 3-Arm A: Nivolumab + Ipilimumab; Part 4-Arm D: Nivolumab + Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (14)

Ucla

Los Angeles, California, 90095, United States

Location

University Of Chicago

Chicago, Illinois, 60637-1443, United States

Location

Sidney kimmel comprehensive cancer center at johns hopkins

Lutherville, Maryland, 21093, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Vanderbilt-Ingram Cancer Ctr

Nashville, Tennessee, 37232, United States

Location

The University Of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Local Institution - 0016

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0008

Pamplona, 31192, Spain

Location

Related Publications (3)

• 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.

  PMID: 33914706 DERIVED

• 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.

  PMID: 33294860 DERIVED

• 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.

  PMID: 30689736 DERIVED

Related Links

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

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 18, 2012
• Study Start: September 27, 2012
• Primary Completion: September 12, 2017
• Study Completion: October 25, 2018
• Last Updated: April 23, 2024
• Results First Posted: December 3, 2019

Record last verified: 2024-04

Locations

NL (1); ES (1); US (12)