An Investigational Immuno-therapy Study of Nivolumab Combined With Ipilimumab Compared to Nivolumab by Itself After Complete Surgical Removal of Stage IIIb/c/d or Stage IV Melanoma (CheckMate 915)

A Phase 3, Randomized Study of Adjuvant Immunotherapy With Nivolumab Combined With Ipilimumab Versus Nivolumab Monotherapy After Complete Resection of Stage IIIb/c/d or Stage IV Melanoma

The purpose of this study is to determine whether an investigational immunotherapy Nivolumab, when combined with Ipilimumab, is more effective than Nivolumab by itself, in delaying the return of cancer in patients who have had a complete surgical removal of stage IIIb/c/d or stage IV Melanoma

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: nivolumab; Biological: ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 1844
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Local Institution
    • Waratah, New South Wales, Australia, 2298
      • Local Institution
    • Westmead, New South Wales, Australia, 2145
      • Local Institution
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution
    • Southport, Queensland, Australia, 4215
      • Local Institution
    • Woolloongabba, Queensland, Australia, 4120
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Local Institution
    • Melbourne, Victoria, Australia, 3004
      • Local Institution
    • Melbourne, Victoria, Australia, 3000
      • Local Institution
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution
    • Subiaco, Western Australia, Australia, 6008
      • Local Institution
• Austria
  • Graz, Austria, 8036
    • Local Institution
  • Wien, Austria, 1090
    • Local Institution
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution
  • Bruxelles, Belgium, 1200
    • Local Institution
  • Gent, Belgium, B-9000
    • Local Institution
  • Liege, Belgium, 4000
    • Local Institution
• Brazil
  • Rio De Janeiro, Brazil, 20220-410
    • Local Institution
  • Rio de Janeiro, Brazil, 22793-080
    • Local Institution
  • Sao Paulo, Brazil, 01246-000
    • Local Institution
  • Bahia
    • Salvador, Bahia, Brazil, 41950-610
      • Local Institution
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Local Institution
  • RIO Grande DO SUL
    • Ijui, RIO Grande DO SUL, Brazil, 98700-000
      • Local Institution
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90610-000
      • Local Institution
  • SAO Paulo
    • Sao Jose do Rio Preto, SAO Paulo, Brazil, 15090-000
      • Local Institution
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88034-000
      • Local Institution
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14780-070
      • Local Institution
• Canada
  • Quebec, Canada, G1R 2J6
    • CHU de Québec - Université Laval
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution
    • Montreal, Quebec, Canada, H2L 4M1
      • Local Institution
• Czechia
  • Brno, Czechia, 656 53
    • Klinika komplexni onkologicke pece
  • Hradec Kralove, Czechia, 500 05
    • Klinika onkologie a radioterapie
  • Praha 10, Czechia, 100 34
    • Dermatovenerologicka klinika 3. LF UK a FNKV
  • Praha 2, Czechia, 128 08
    • Dermatovenerologicka klinika VFN a 1. LF UK
• France
  • Dijon, France, 21079
    • Centre Hospitalier Universitaire Dijon Bocage
  • LILLE Cedex, France, 59037
    • Hôpital Claude Huriez
  • Marseille Cedex 5, France, 13385
    • Hôpital de la Timone
  • Nantes, France, 44093
    • Chu Nantes
  • Paris, France, 75475
    • Hopital Saint Louis
  • Pierre Benite Cedex, France, 69495
    • Centre Hospitalier Lyon Sud
  • Toulouse Cedex 9, France, 31059
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 10117
    • Local Institution
  • Buxtehude, Germany, 21614
    • Local Institution
  • Essen, Germany, 45147
    • Local Institution
  • Gera, Germany, 07548
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
  • Heidelberg, Germany, 69120
    • Local Institution
  • Luebeck, Germany, 23538
    • Local Institution
  • Muenchen, Germany, 80337
    • Local Institution
  • Tuebingen, Germany, 72076
    • Local Institution
• Greece
  • Athens, Greece, 18547
    • Metropolitan Hospital
  • Athens, Greece, 11527
    • Laiko Hospital
• Israel
  • Haifa, Israel, 3109601
    • Local Institution
  • Jerusalem, Israel, 91120
    • Local Institution
  • Tel Hashomer, Israel, 52621
    • Local Institution
• Italy
  • Bergamo, Italy, 24127
    • Asst Papa Giovanni Xxiii
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino
  • Milano, Italy, 20133
    • IRCCS Istituto Nazionale Tumori Milano
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto IOV
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
• New Zealand
  • Christchurch, New Zealand
    • Local Institution
  • Dunedin, New Zealand, 9001
    • Local Institution
  • BAY OF Plenty
    • Tauranga, BAY OF Plenty, New Zealand, 3143
      • Local Institution
• Poland
  • Krakow, Poland, 31-115
    • Klinika Nowotworow Ukladowych i Uogolnionych
  • Warszawa, Poland, 02-781
    • Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków
• Romania
  • Bucharest, Romania, 022328
    • Institute Of Oncology "Prof.Dr.Alexandru Trestioreanu" Bucha
  • Craiova, Romania, 200347
    • Sf. Nectarie Oncology Center
• Russian Federation
  • Krasnodar, Russian Federation, 350040
    • Local Institution
  • Krasnoyarsk, Russian Federation, 660133
    • Local Institution
  • Moscow, Russian Federation, 115478
    • Local Institution
• Spain
  • Badalona-barcelona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08035
    • H. Univ. Vall dHebron
  • Madrid, Spain, 28007
    • Hospital Gral. Univ. Gregorio Maranon
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Sevilla, Spain, 41009
    • Hosp Univ Virgen Macarena
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La FE
• Switzerland
  • Lausanne, Switzerland, 1011
    • Local Institution
  • Zuerich, Switzerland, 8091
    • Local Institution
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital Nhs Trust
  • Sutton., United Kingdom, SM25PT
    • Royal Marsden Hospital - Surrey
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
      • Local Institution
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic & Research Institute
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Med Ctr
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • UF Health Cancer Center at Orlando Health
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 19123
      • University of Chicago
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, S.C.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Mass General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5848
      • University of Michigan Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Nassau
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Med Ctr
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center Oncology And Hematology Care
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • St. Luke's University Health Network
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Local Institution
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology Sammons Cancer Center
    • Houston, Texas, United States, 77030-4009
      • Md Anderson Can Cnt
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Fairfax, Virginia, United States, 55905
      • Inova Melanoma and Skin Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • University Of Washington Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Completely surgically resected stage IIIb/c/d or stage IV melanoma within 12 weeks of participation in study.
• Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work
• No prior anti-cancer treatment for melanoma (except surgery for the melanoma lesion(s) and/or except for adjuvant radiation therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions)

Exclusion Criteria:

• History of uveal melanoma
• Patients with active, known or suspected autoimmune disease
• Prior treatment with interferon (if complete < 6 months prior to participation in study), anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nivolumab + ipilimumab; Specified Dose on Specified Days	Biological: nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo; Biological: ipilimumab; Specified Dose on Specified Days; Other Names: BMS-734016; Yervoy
Experimental: nivolumab; Specified Dose on Specified Days	Biological: nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival (RFS) - All Randomized Participants	RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first. Median values based on Kaplan-Meier Estimates.	From randomization to Primary Completion Date (up to approximately 3 years)
Recurrence-free Survival (RFS) - All Randomized Participants With PD-L1 Expression Level < 1%	RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first. Median based on Kaplan-Meier Estimates.	From randomization to Primary Completion Date (up to approximately 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) - All Randomized Participants	OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates.	From randomization to date of death (up to approximately 45 months)
Overall Survival (OS) - All Randomized Participants With PD-L1 Expression Level < 1%	OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates.	From randomization to date of death (up to approximately 45 months)
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression	RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first. Median based on Kaplan-Meier Estimates.	From randomization to Study Completion Date (up to approximately 45 months)
Time to Next-Line Therapies - All Randomized Participants	Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date. Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date.	From randomization to start of next therapy or second next therapy (up to approximately 45 months)
Time to Next-Line Therapies - All Randomized Participants With PD-L1 Expression Level < 1%	Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date. Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date	From randomization to start of next therapy or second next therapy (up to approximately 45 months)
Time From Next Therapy to Second Next Therapy - All Randomized Participants	Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment.	From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months)
Time From Next Therapy to Second Next Therapy - All Randomized Participants With PD-L1 Expression Level < 1%	Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment.	From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months)
Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants	PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death.	From randomization to progression event (up to approximately 45 months)
Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants With PD-L1 Expression Level < 1%	PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death.	From randomization to progression event (up to approximately 45 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Weber JS, Schadendorf D, Del Vecchio M, Larkin J, Atkinson V, Schenker M, Pigozzo J, Gogas H, Dalle S, Meyer N, Ascierto PA, Sandhu S, Eigentler T, Gutzmer R, Hassel JC, Robert C, Carlino MS, Di Giacomo AM, Butler MO, Munoz-Couselo E, Brown MP, Rutkowski P, Haydon A, Grob JJ, Schachter J, Queirolo P, de la Cruz-Merino L, van der Westhuizen A, Menzies AM, Re S, Bas T, de Pril V, Braverman J, Tenney DJ, Tang H, Long GV. Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915). J Clin Oncol. 2023 Jan 20;41(3):517-527. doi: 10.1200/JCO.22.00533. Epub 2022 Sep 26.
• Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. doi: 10.1200/JCO.21.02628. Epub 2022 May 5.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2017
• Primary Completion (Actual): June 12, 2020
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: February 27, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): September 20, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-915; 2016-003729-41 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No