Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line Treatment for Patients With Advanced Melanoma (CheckMate 401)

Clinical Trial of Nivolumab (BMS-936558) Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line Therapy of Subjects With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma CheckMate 401: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 401

The purpose of this study is to determine the effects of combination treatment of Nivolumab with Ipilimumab followed by Nivolumab monotherapy in patients with previously untreated advanced Melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Ipilimumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 533
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Local Institution
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution
    • Coffs Harbour, New South Wales, Australia, 2450
      • Local Institution
    • Gateshead, New South Wales, Australia, 2290
      • Local Institution
    • North Sydney, New South Wales, Australia, 2060
      • Local Institution
  • Northern Territory
    • Tiwi, Northern Territory, Australia, 0810
      • Local Institution
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Local Institution
    • Cairns, Queensland, Australia, 4870
      • Local Institution
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution
    • Southport, Queensland, Australia, 4215
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
    • Bedford Park, South Australia, Australia, 5402
      • Local Institution
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Local Institution
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Local Institution
    • Melbourne, Victoria, Australia, 3128
      • Local Institution
    • Melbourne, Victoria, Australia, 3144
      • Local Institution
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution
• Austria
  • Graz, Austria, 8036
    • Local Institution
  • Innsbruck, Austria, 6020
    • Local Institution
  • Salzburg, Austria, 5020
    • Local Institution
  • Vienna, Austria, 1090
    • Local Institution
• Belgium
  • Brussel, Belgium, 1090
    • Local Institution
  • Bruxelles, Belgium, 1200
    • Local Institution
• Finland
  • Helsinki, Finland, 00290
    • Local Institution
  • Oulu, Finland, 90029
    • Local Institution
  • Tampere, Finland, 33520
    • Local Institution
  • Turku, Finland, FIN-20520
    • Local Institution
• France
  • Angers Cedex 9, France, 49933
    • Local Institution
  • Bordeaux, France, 33075
    • Local Institution
  • Boulogne Billancourt, France, 92104
    • Local Institution
  • Clermont-Ferrand, France, 63003
    • Local Institution
  • Dijon, France, 21079
    • Local Institution
  • Grenoble Cedex 09, France, 38043
    • Local Institution
  • Le Mans Cedex 9, France, 72037
    • Local Institution
  • Lille, France, 59037
    • Local Institution
  • Marseille, France, 13385
    • Local Institution
  • Montpellier, France, 34295
    • Local Institution
  • Nantes Cedex 01, France, 44093
    • Local Institution
  • Nice, France, 06202
    • Local Institution
  • Paris, France, 75010
    • Local Institution
  • Pierre Benite Cedax, France, 69495
    • Local Institution
  • Rennes Cedex, France, 35042
    • Local Institution
  • Rouen Cedex, France, 76031
    • Local Institution
  • TOULOUSE Cedex 9, France, 31059
    • Local Institution
  • Vandoeuvre-les-Nancy, France, 54511
    • Local Institution
  • Villejuif, France, 94805
    • Local Institution
• Germany
  • Berlin, Germany, 10117
    • Local Institution
  • Dresden, Germany, 01277
    • Local Institution
  • Erfurt, Germany, 99028
    • Local Institution
  • Erlangen, Germany, 91054
    • Local Institution
  • Frankfurt, Germany, 60590
    • Local Institution
  • Freiburg, Germany, 79104
    • Local Institution
  • Gottingen, Germany, 37075
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
  • Kiel, Germany, 24105
    • Local Institution
  • Leipzig, Germany, 04103
    • Local Institution
  • Ludwigshafen, Germany, 67063
    • Local Institution
  • Luebeck, Germany, 23538
    • Local Institution
  • Mannheim, Germany, 68167
    • Local Institution
  • Regensburg, Germany, 93053
    • Local Institution
  • Schwerin, Germany, 19049
    • Local Institution
  • Stade, Germany, 21682
    • Local Institution
  • Rhineland-palladium
    • Mainz, Rhineland-palladium, Germany, 55131
      • Local Institution
• Ireland
  • Cork, Ireland
    • Local Institution
  • Dublin, Ireland, 4
    • Local Institution
  • Dublin, Ireland, 8
    • Local Institution
  • Dublin, Ireland, 7
    • Local Institution
  • Dublin, Ireland, 9
    • Local Institution
  • Galway, Ireland, ST4 6QG
    • Local Institution
• Italy
  • Bari, Italy, 70124
    • Local Institution
  • Bergamo, Italy, 24127
    • Local Institution
  • Genova, Italy, 16132
    • Local Institution
  • Meldola, Italy, 47014
    • Local Institution
  • Milan, Italy, 20141
    • Local Institution
  • Milano, Italy, 20133
    • Local Institution
  • Napoli, Italy, 80131
    • Local Institution
  • Padova, Italy, 35128
    • Local Institution
  • Pisa, Italy, 56126
    • Local Institution
  • Roma, Italy
    • Local Institution
  • Roma, Italy, 00144
    • Local Institution
  • Siena, Italy, 53100
    • Local Institution
  • Terni, Italy, 05100
    • Local Institution
  • Torino, Italy, 10126
    • Local Institution
• Norway
  • Oslo, Norway, 0424
    • Local Institution
  • Stavanger, Norway, 4011
    • Local Institution
• Sweden
  • Eskilstuna, Sweden, 631 88
    • Local Institution
  • Gävle, Sweden, SE-80187
    • Local Institution
  • Karlskrona, Sweden, 371 85
    • Local Institution
  • Linköping, Sweden, SE-58185
    • Local Institution
  • Stockholm, Sweden, 17176
    • Local Institution
  • Sundsvall, Sweden, 164 40
    • Local Institution
  • Vasteras, Sweden, 721 89
    • Local Institution
  • Växjö, Sweden, SE-35185
    • Local Institution
• Switzerland
  • Basel, Switzerland, 4031
    • Local Institution
  • Lausanne, Switzerland, 1005
    • Local Institution
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Local Institution
  • Cottingham, United Kingdom, HU16 5JQ
    • Local Institution
  • Glasgow, United Kingdom, G12 0YN
    • Local Institution
  • Headington, United Kingdom, OX3 7LE
    • Local Institution
  • London, United Kingdom, SE1 9RT
    • Local Institution
  • Manchester, United Kingdom, M20 4BX
    • Local Institution
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Local Institution
  • Preston, United Kingdom, PR2 9HT
    • Local Institution
  • Sheffield, United Kingdom, S10 2SJ
    • Local Institution
  • Southampton, United Kingdom, SO16 6YD
    • Local Institution
  • Swansea, United Kingdom, SA2 8QA
    • Local Institution
  • Truro, United Kingdom, TR1 3LJ
    • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Potential subjects must have advanced Melanoma (stage III or IV as confirmed by biopsy) with spread to other sites in the body and unable to be removed by surgery.
• Potential subjects must be newly diagnosed with advanced melanoma and received no treatment for the advanced disease.

NOTE: Prior adjuvant or neoadjuvant melanoma therapy (including anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, such as anti-CD-137) is permitted if the therapy was used in the adjuvant or neoadjuvant setting but not in the metastatic setting. These drugs must be discontinued 6 months prior to study entry and the side effects related to the prior therapy resolved.

• Potential subjects (with disease spread to brain) who previously received primary treatment are permitted if there was no evidence of disease as confirmed by the MRI (at least 2 weeks after the primary treatment is complete and with in 6 weeks of the first dose of the study drug). Potential subjects must not have received intravenous steroid treatment (>10 mg/day) intravenously for at least 2 weeks prior to study drug administration.

Exclusion Criteria:

• Leptomenigeal metastases
• Subjects with autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• All side effects from previous primary treatments other than alopecia, fatigue, or peripheral neuropathy must have resolved to Grade 1 or baseline before administration of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Combination therapy: Nivolumab + Ipilimumab; Nivolumab + Ipilimumab specified dose on specified days	Drug: Ipilimumab; Drug: Nivolumab
EXPERIMENTAL: Monotherapy: Nivolumab; Nivolumab specified dose on specified days	Drug: Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events	Incidence of participants with high-grade (CTCAE v4.0 grade 3-5) treatment-related, select adverse events of potentially immune-mediated etiology including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity	From first dose to 30 days after last dose (up to approximately 37 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events	Incidence of participants with high-grade (grade 3-5) select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, infusion-related, or hypersensitivity	From first dose to 30 days after last dose (up to approximately 37 months)
Median Time to Onset (Grades 3-4) of Select Adverse Events	Median time to onset (grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity	From first dose to 30 days after last dose (up to approximately 37 months)
Median Time to Resolution (Grades 3-4) of Select Adverse Events	Median time to resolution (Grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity	From first dose to 30 days after last dose (up to approximately 37 months)
Time to Resolution of an Adverse Event (AE)	Resolution of an adverse event (AE) is defined as a participant experiencing complete resolution or improvement to the baseline of any grade AE including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity	From first dose to 30 days after last dose (up to approximately 37 months)
Overall Survival (OS)	Overall survival is defined from the time of first dosing date to the date of death. A participant who has not died will be censored at the last known date alive	Up to approximately 37 months
Incidence of Participants With Adverse Events	The assessment of safety is measured by the incidence of participants who experienced any grade of adverse events (AEs), treatment-related AEs, serious adverse events (SAEs), and deaths	From first dose to 30 days after last dose (up to approximately 37 months)
Incidence of Participants With Select Adverse Events	The assessment of safety is measured by the incidence of participants who experienced any grade of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity	From first dose to 30 days after last dose (up to approximately 37 months)
Incidence of Participants With Laboratory Abnormalities - Liver	Safety assessment is measured by the incidence of participants who experienced a liver laboratory abnormality in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Upper Limit of Normal (ULN)	From first dose to 30 days after last dose (up to approximately 37 months)
Incidence of Participants With Laboratory Abnormalities - Thyroid	Safety assessment is measured by the incidence of participants who experienced a thyroid laboratory abnormality in Free T3 (FT3), Free T4 (FT4), Lower Limit of Normal (LLN)	From first dose to 30 days after last dose (up to approximately 37 months)
Objective Response Rate (ORR)	Objective response rate is defined as the percentage of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of all treated participants	Up to approximately 37 months
Progression Free Survival (PFS)	Progression free survival per investigator assessment is defined as radiological evidence of progression, significant clinical symptomatic progression, or the need to introduce a non-study drug therapy.	Up to approximately 37 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

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): December 20, 2015
• Primary Completion (ACTUAL): February 10, 2020
• Study Completion (ACTUAL): February 10, 2020

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (ESTIMATE): November 6, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 15, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 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: CA209-401; 2015-001274-17 (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
• product manufactured in and exported from the U.S.: Yes