Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma

NCT ID: NCT01927419

Last Updated: 2022-03-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-23

Study Completion Date

2021-02-26

Brief Summary

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The primary purpose of this study is to compare the objective response rate, as determined by investigators, of Nivolumab combined with Ipilimumab versus Ipilimumab monotherapy in patients with untreated, unresectable, or metastatic melanoma

Detailed Description

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Conditions

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Unresectable Melanoma Metastatic Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Nivolumab + Ipilimumab

Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Ipilimumab

Intervention Type DRUG

Placebo + Ipilimumab

Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type DRUG

Placebo

Intervention Type DRUG

Matching nivolumab

Interventions

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Nivolumab

Intervention Type DRUG

Ipilimumab

Intervention Type DRUG

Placebo

Matching nivolumab

Intervention Type DRUG

Other Intervention Names

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Opdivo, BMS-936558 Yervoy

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group performance status of 0 or 1
* Histologically confirmed unresectable Stage III or Stage IV melanoma
* No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
* Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
* Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.

Exclusion Criteria

* Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (\>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
* Ocular melanoma
* Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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San Francisco Oncology Associates

San Francisco, California, United States

Site Status

Orlando Health Inc

Orlando, Florida, United States

Site Status

University Of Louisville Medical Center, Inc., Dba

Louisville, Kentucky, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Washington University School Of Medicine

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers Of Nevada

Las Vegas, Nevada, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

University Of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

NYU Clinical Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Nassau

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

The Christ Hospital

Cincinnati, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

St. Luke's Hospital

Easton, Pennsylvania, United States

Site Status

GHS Cancer Institute

Greenville, South Carolina, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

University Of Wisconsin Paul P Carbone Comprehensive Ca Ctr

Madison, Wisconsin, United States

Site Status

Hopital Larrey

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Countries

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United States France

References

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Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.

Reference Type DERIVED
PMID: 39504507 (View on PubMed)

Mantia CM, Werner L, Stwalley B, Ritchings C, Tarhini AA, Atkins MB, McDermott DF, Regan MM. Sensitivity of treatment-free survival to subgroup analyses in patients with advanced melanoma treated with immune checkpoint inhibitors. Melanoma Res. 2022 Feb 1;32(1):35-44. doi: 10.1097/CMR.0000000000000793.

Reference Type DERIVED
PMID: 34855329 (View on PubMed)

Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1558-1568. doi: 10.1016/S1470-2045(16)30366-7. Epub 2016 Sep 9.

Reference Type DERIVED
PMID: 27622997 (View on PubMed)

Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015 May 21;372(21):2006-17. doi: 10.1056/NEJMoa1414428. Epub 2015 Apr 20.

Reference Type DERIVED
PMID: 25891304 (View on PubMed)

Related Links

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Other Identifiers

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2013-002018-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-069

Identifier Type: -

Identifier Source: org_study_id

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