Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma

NCT01721772 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-0662012-003718-16
• Study Type: interventional
• Target: 418
• Locations: 16 countries
• Sites: 75

Brief Summary

The purpose of this study is to compare the clinical benefit, as measured by overall survival, of nivolumab with that of. dacarbazine in patients with previously untreated, unresectable, or metastatic melanoma

Conditions

Melanoma

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  OS is defined as the time between the date of randomization and the date of death or the last date the participant was known to be alive.

  From date of randomization to date of death. For those without documentation of death, to the last date the participant was known to be alive, assessed up to 17 months.

• Overall Survival (OS) Rate

  OS rate is calculated as the percentage of participants alive at the indicated timepoints

  From randomization to 6 months and or to 12 months

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  From date of randomization up to date of disease progression or death, up to approximately 84 months

• Progression-free Survival (PFS) Rate

  From randomization to the specified timepoints, up to 84 months

• Objective Response Rate (ORR)

  Tumor assessments beginning at 9 weeks following randomization and continuing every 6 weeks for the first year, then every 12 weeks thereafter until disease progression or death, assessed to 94 months

• Overall Survival by Programmed Cell Death Ligand 1 (PD-L1) Expression Level

  From date of randomization to date of disease progression or death, up to approximately 94 months

• Change From Baseline in Health-related Quality of Life (HRQoL) Scores

  At baseline and every 6 weeks for 12 months and at follow-up visits 1 and 2, assessed up to 93 months

Study Arms (2)

Nivolumab, 3 mg/kg

EXPERIMENTAL

Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may switch to nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.

Biological: BMS-936558 (Nivolumab); Drug: Placebo matching Dacarbazine

Dacarbazine, 1000 mg/m^2

ACTIVE COMPARATOR

Participants received dacarbazine, 1000 mg/m\^2, solution administered IV every 3 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may cross-over to nivolumab open label treatment, either 3 mg/kg every 2 weeks or 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.

Biological: Placebo matching BMS-936558 (Nivolumab); Drug: Dacarbazine

Interventions

BMS-936558 (Nivolumab) BIOLOGICAL

Nivolumab, 3 mg/kg

Placebo matching BMS-936558 (Nivolumab) BIOLOGICAL

Dacarbazine, 1000 mg/m^2

Dacarbazine DRUG

Dacarbazine, 1000 mg/m^2

Placebo matching Dacarbazine DRUG

Nivolumab, 3 mg/kg

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 of age
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Untreated and histologically confirmed unresectable Stage III or Stage IV melanoma, as per the staging system of the American Joint Committee on Cancer
• Measurable disease as per Response Evaluation Criteria in Solid Tumors 1.1
• Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses
• Known BRAF wild-type, as per regionally acceptable V600 mutational status testing. BRAF mutant patients and those with indeterminate or unknown BRAF status are not permitted to randomize

You may not qualify if:

• Active brain metastases or leptomeningeal metastases
• Ocular melanoma
• Any active, known, or suspected autoimmune disease

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (75)

Fundacion Cidea

Buenos Aires, Distrito Federal, 1121, Argentina

Location

Instituto Medico Especialazado Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Instituto Oncologico De Cordoba

Córdoba, 5000, Argentina

Location

Local Institution

Camperdown, New South Wales, 2050, Australia

Location

Coffs Harbour Health Campus

Coffs Harbour, New South Wales, 2450, Australia

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Local Institution - 0006

North Sydney, New South Wales, 2060, Australia

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Local Institution

Westmead, New South Wales, 2145, Australia

Location

Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

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Local Institution

Southport, Queensland, 4215, Australia

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Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

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Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

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Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 0039

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Qe Ii Health Science Centre

Halfax, Nova Scotia, B3H 2Y9, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

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Local Institution - 0040

Montreal, Quebec, H4A 3J1, Canada

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Local Institution

Viña del Mar, Región de Valparaíso, Chile

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Santiago, Santiago Metropolitan, Chile

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Local Institution

Santiago, 7630370, Chile

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Aarhus Universitetshospital

Aarhus, 8000, Denmark

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Herlev Hospital

Herlev, 2730, Denmark

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Odense University Hospital

Odense, 5000, Denmark

Location

Local Institution - 0035

Helsinki, 00290, Finland

Location

Hopital Saint Andre

Bordeaux, 33075, France

Location

Chu Grenoble - Hopital Albert Michallon

Grenoble, 38043, France

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Chru De Lille - Hopital Claude Huriez

Lille, 59037, France

Location

Hopital St Eloi

Montpellier, 34295, France

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Hopital Saint Louis

Paris, 75010, France

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Local Institution - 0013

Villejuif, 94805, France

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Würzburg, Bavaria, 97080, Germany

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Cologne, 50937, Germany

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Essen, 45122, Germany

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Gera, 07548, Germany

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Göttingen, 37075, Germany

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Heidelberg, 69120, Germany

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Kiel, 24105, Germany

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Magdeburg, 39120, Germany

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Mainz, 55131, Germany

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Nuremberg, 90419, Germany

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Recklinghausen, 45659, Germany

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Tübingen, 72076, Germany

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Laiko Hospital

Athens, 11527, Greece

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Metropolitan Hospital

Neo Faliro, 18547, Greece

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Haifa, 34362, Israel

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Jerusalem, 91120, Israel

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Tel Litwinsky, 52621, Israel

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Bari, 70124, Italy

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Bergamo, 24127, Italy

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Genova, 16132, Italy

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Meldola (fc), 47014, Italy

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Milan, 20133, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Padua, 35128, Italy

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Roma, 00144, Italy

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Siena, 53100, Italy

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Leon, Guanajato, Guanajuato, 37000, Mexico

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Mexico City, Mexico City, 03310, Mexico

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Tlalpan, Mexico City, 14080, Mexico

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Morelia, Michoacán, 58240, Mexico

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Oslo, 0379, Norway

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Gdansk, 80-219, Poland

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Lodz, 93-513, Poland

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Warsaw, 02-781, Poland

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Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Local Institution - 0056

Barcelona, 08036, Spain

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Madrid, 28033, Spain

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Madrid, 28034, Spain

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Seville, 41009, Spain

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Valencia, 46014, Spain

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Gothenberg, 413 45, Sweden

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Lund, 221 85, Sweden

Location

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Umeå, 901 85, Sweden

Location

Related Publications (6)

• 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.

  PMID: 39504507 DERIVED

• Robert C, Long GV, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, Rutkowski P, Hassel JC, McNeil CM, Kalinka EA, Lebbe C, Charles J, Hernberg MM, Savage KJ, Chiarion-Sileni V, Mihalcioiu C, Mauch C, Arance A, Cognetti F, Ny L, Schmidt H, Schadendorf D, Gogas H, Zoco J, Re S, Ascierto PA, Atkinson V. Five-Year Outcomes With Nivolumab in Patients With Wild-Type BRAF Advanced Melanoma. J Clin Oncol. 2020 Nov 20;38(33):3937-3946. doi: 10.1200/JCO.20.00995. Epub 2020 Sep 30.

  PMID: 32997575 DERIVED

• Ascierto PA, Long GV, Robert C, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbe C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Ny L, Arance A, Svane IM, Schadendorf D, Gogas H, Saci A, Jiang J, Rizzo J, Atkinson V. Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial. JAMA Oncol. 2019 Feb 1;5(2):187-194. doi: 10.1001/jamaoncol.2018.4514.

  PMID: 30422243 DERIVED

• Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G, Rashford M, Agrawal S, Grigoryeva E, Bello A, Roy A, Rollin L, Zhao X. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018 Nov 1;29(11):2208-2213. doi: 10.1093/annonc/mdy408.

  PMID: 30215677 DERIVED

• Long GV, Weber JS, Larkin J, Atkinson V, Grob JJ, Schadendorf D, Dummer R, Robert C, Marquez-Rodas I, McNeil C, Schmidt H, Briscoe K, Baurain JF, Hodi FS, Wolchok JD. Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials. JAMA Oncol. 2017 Nov 1;3(11):1511-1519. doi: 10.1001/jamaoncol.2017.1588.

  PMID: 28662232 DERIVED

• Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbe C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320-30. doi: 10.1056/NEJMoa1412082. Epub 2014 Nov 16.

  PMID: 25399552 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Dacarbazine

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; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

An independent data monitoring committee (DMC) found that data from a DMC-requested database lock showed clear survival benefit with nivolumab and thus recommended unblinding the study and switching patients randomized to dacarbazine to nivolumab.

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 6, 2012
• Study Start: January 18, 2013
• Primary Completion: June 24, 2014
• Study Completion: May 14, 2021
• Last Updated: July 12, 2022
• Results First Posted: February 25, 2016

Record last verified: 2022-06

Locations

AR (3); CA (6); FI (1); DE (12); PL (3); IT (10); SE (3); CL (3); FR (6); AU (9); DK (3); ES (6); NO (1); GR (2); IL (3); ME (4)