A Dose Frequency Optimization,Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received Up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks (CheckMate 384)

A Dose Frequency Optimization, Phase IIIB/IV Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks

The primary objective of this study is to compare PFS (progression-free survival) rate at 6 months and at 1 year after randomization, of Nivolumab 480 mg every 4 weeks with nivolumab 240 mg every 2 weeks in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Local Institution - 0052
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 0118
    • Westmead,, New South Wales, Australia, 2145
      • Local Institution - 0117
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Local Institution - 0093
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Local Institution - 0054
    • Elizabeth Vale, South Australia, Australia, 5112
      • Local Institution - 0056
    • Kurralta Park, South Australia, Australia, 5037
      • Local Institution - 0055
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Local Institution - 0057
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0053
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution - 0058
• Austria
  • Wien, Austria, 1090
    • Local Institution
• Canada
  • Quebec, Canada, GIJ 1Z4
    • Local Institution
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Local Institution - 0059
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Local Institution - 0146
    • Montreal, Quebec, Canada, H4J 1C5
      • Local Institution - 0145
    • St. Jerome, Quebec, Canada, J7Z 5T3
      • Local Institution - 0060
• France
  • Angers, France, 49000
    • Local Institution - 0081
  • Angers, France, 49000
    • Local Institution - 0105
  • Bayonne, France, 64109
    • Local Institution - 0080
  • Clermont-Ferrand Cedex 01, France, 63003
    • Local Institution - 0076
  • Le Mans, France, 72000
    • Local Institution - 0077
  • Mulhouse, France, 68100
    • Local Institution - 0072
  • Nimes, France, 30029
    • Local Institution - 0078
  • Paris, France, 75005
    • Local Institution - 0095
  • Paris, France, 75014
    • Local Institution - 0083
  • Pontoise, France, 95300
    • Local Institution
  • Suresnes Cedex, France, 92 151
    • Local Institution - 0075
  • Tours, France, 37044
    • Local Institution - 0079
  • Vandoeuvre-les-Nancy, France, 54519
    • Local Institution - 0097
  • Villefranche-sur-Saone Cedex, France, 69655
    • Local Institution - 0096
• Germany
  • Bad Berka, Germany, 99437
    • Local Institution
  • Berlin, Germany, 13353
    • Local Institution - 0073
  • Dresden, Germany, 01307
    • Local Institution - 0063
  • Freiburg, Germany, 79106
    • Local Institution
  • Gauting, Germany, 82131
    • Local Institution - 0102
  • Greifenstein, Germany, 35753
    • Local Institution - 0062
  • Hamburg, Germany, 20251
    • Local Institution - 0061
  • Hannover, Germany, 30625
    • Local Institution - 0113
  • Kassel, Germany, 34125
    • Local Institution - 0064
  • Kiel, Germany, 24105
    • Local Institution - 0106
  • Leipzig, Germany, 04357
    • Local Institution - 0065
  • Lostau, Germany, 39291
    • Local Institution
  • Moers, Germany, 47447
    • Local Institution - 0066
  • Nürnberg, Germany, 90419
    • Local Institution - 0067
• Italy
  • Localita San Filippo Lucca, Italy, 55100
    • Local Institution - 0086
  • Monza, Italy, 20900
    • Local Institution - 0085
  • Napoli, Italy, 80131
    • Local Institution - 0088
  • Roma, Italy, 00128
    • Local Institution - 0087
• Spain
  • Barcelona, Spain, 08208
    • Local Institution - 0069
  • El Palmar, Spain, 30120
    • Local Institution - 0104
  • Las Palmas de Gran Canaria, Spain, 35016
    • Local Institution - 0068
  • Sevilla, Spain, 41013
    • Local Institution - 0070
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Local Institution - 0004
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Local Institution - 0030
    • Phoenix, Arizona, United States, 85016
      • Local Institution - 0041
  • California
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc.
    • Bellflower, California, United States, 90706
      • Southern California Permanente Medical Group
    • Fullerton, California, United States, 92835
      • St Jude Hospital Yorba Linda
    • Los Angeles, California, United States, 90095
      • Local Institution - 0046
    • Orange, California, United States, 92868
      • Local Institution - 0126
    • Redondo Beach, California, United States, 90227
      • Torrance Health Association
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • Santa Barbara, California, United States, 93015
      • Local Institution - 0010
    • Santa Maria, California, United States, 93454
      • Local Institution - 0044
    • Vallejo, California, United States, 94589
      • Local Institution - 0130
  • Colorado
    • Denver, Colorado, United States, 80218-1210
      • Local Institution - 0017
    • Fort Collins, Colorado, United States, 80528
      • Local Institution - 0122
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Local Institution - 0038
    • Hollywood, Florida, United States, 33021
      • Local Institution - 0089
    • Ocala, Florida, United States, 34471
      • Local Institution - 0026
    • Pensacola, Florida, United States, 32504
      • Local Institution - 0001
    • Saint Petersburg, Florida, United States, 33705
      • Local Institution - 0039
  • Georgia
    • Athens, Georgia, United States, 30607
      • Local Institution - 0008
    • Columbus, Georgia, United States, 31904
      • Local Institution - 0142
    • Marietta, Georgia, United States, 30060
      • Local Institution - 0121
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Health System
    • Niles, Illinois, United States, 60714
      • Local Institution - 0098
    • Peoria, Illinois, United States, 61615
      • Local Institution - 0100
    • Urbana, Illinois, United States, 61801-2594
      • Local Institution - 0143
  • Indiana
    • Fort Wayne, Indiana, United States, 46485
      • Local Institution - 0099
    • Fort Wayne, Indiana, United States, 46804
      • Local Institution - 0050
    • Indianapolis, Indiana, United States, 46237
      • Innova Schar Cancer Institute
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Local Institution - 0123
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Local Institution - 0112
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • New Orleans, Louisiana, United States, 70121
      • Local Institution - 0137
  • Maine
    • Brewer, Maine, United States, 04412
      • Local Institution - 0109
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Local Institution - 0042
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Local Institution - 0125
  • Michigan
    • Southfield, Michigan, United States, 48075
      • Local Institution - 0136
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Local Institution - 0120
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Local Institution - 0116
  • Missouri
    • Springfield, Missouri, United States, 65806
      • Mercy Medical Research Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Local Institution - 0014
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Local Institution - 0141
  • New York
    • Albany, New York, United States, 12206
      • Local Institution - 0035
    • Johnson City, New York, United States, 13790
      • Local Institution - 0013
  • North Carolina
    • Pinehurst, North Carolina, United States, 28374
      • Local Institution - 0127
  • Ohio
    • Canton, Ohio, United States, 44708
      • Hematology and Oncology Associates
    • Cincinnati, Ohio, United States, 45242
      • Local Institution - 0037
    • Cincinnati, Ohio, United States, 45242
      • Local Institution - 0132
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Cancer Care Center
    • Massillon, Ohio, United States, 44646
      • Local Institution - 0129
  • Oregon
    • Medford, Oregon, United States, 97504
      • Hematology Oncology Consultants, Pc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Local Institution - 0005
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Local Institution - 0020
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Local Institution - 0124
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Jones Clinic PC
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0036
  • Texas
    • Abilene, Texas, United States, 79606-5208
      • Local Institution - 0023
    • Amarillo, Texas, United States, 79106
      • Texas Oncology - Amarillo
    • Dallas, Texas, United States, 75230
      • Local Institution - 0011
    • Dallas, Texas, United States, 75231
      • Local Institution - 0022
    • Denton, Texas, United States, 76210
      • Texas Oncology, P.A.
    • El Paso, Texas, United States, 79902
      • Texas Oncology, P.A.
    • Flower Mound, Texas, United States, 75028
      • Local Institution - 0025
    • Houston, Texas, United States, 77024
      • Texas Oncology, P.A.
    • Longview, Texas, United States, 75601
      • Texas Oncology, P.A.
    • Midland, Texas, United States, 79701
      • Local Institution - 0119
    • Plano, Texas, United States, 75093
      • Texas Oncology, P.A.
    • San Antonio, Texas, United States, 78212
      • Texas Oncology, P.A.
    • Sherman, Texas, United States, 75090
      • Texas Oncology, P.A.
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology, P.A.
    • Wichita Falls, Texas, United States, 76310
      • Local Institution - 0034
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Innova Schar Cancer Institute
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology
  • Washington
    • Spokane Valley, Washington, United States, 99216
      • Cancer Care Northwest
    • Vancouver, Washington, United States, 98684
      • Local Institution - 0031
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/North Star Lodge

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 Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histologically or cytologically documented Squamous or non-Squamous Non-small cell lung cancer (NSCLC) (Stage IIIB/IV), or recurrent or progressive disease following multimodal therapy
• Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD)
• Measurable disease before start of pre-study nivolumab treatment
• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2

Exclusion Criteria:

• Carcinomatous meningitis
• Untreated, symptomatic Central nervous system (CNS) metastases
• Symptomatic interstitial lung disease

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
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Nivolumab 240 mg; Nivolumab 240 mg Every 2 Weeks	Biological: Nivolumab
EXPERIMENTAL: Nivolumab 480 mg; Nivolumab 480 mg Every 4 Weeks	Biological: Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Rate (PFSR) at 6 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.	At 6 Months
Progression Free Survival Rate (PFSR) at 12 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.	At 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Rate (PFSR) at 24 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.	At 24 Months
Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.	At 12 Months
Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months	The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	At 12 Months
Overall Survival (OS) Rate at 12 Months	The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.	At 12 Months
Overall Survival (OS) Rate up to 60 Months	The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.	From randomization to the date of death, Up to 60 Months
Overall Survival Rate by Histology at 12 Months	The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. OS rate by histology did not have data collected after 12 months randomization.	at 12 Months
Overall Survival Rate by Response Criteria at 12 Months	The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. OS rate by response did not have data collected after 12 months randomization.	12 Months
Percentage of Participants With an Adverse Events (AEs)	Percentage of participants with an Adverse Event due to any cause An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Percentage of Participants With an Serious Adverse Events (SAEs)	Percentage of participants with an Serious Adverse Event due to any cause. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe); requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed in the definition above.)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC)	Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Percentage of Participants With an Immune Mediated Adverse Events (IMAEs)	Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Percentage of Participants With an Select Adverse Events	Percentage of Participants with an Select Adverse Event due to any cause Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endocrine.	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Percentage of Participants With an Event of Special Interest (ESI)	Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Percentage of Participants Who Experienced Death	Percentage of Participants who experienced Death due to any cause	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)
Number of Participants With Laboratory Test Abnormalities	Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 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): May 24, 2016
• Primary Completion (ACTUAL): July 15, 2019
• Study Completion (ACTUAL): January 18, 2022

Study Registration Dates

• First Submitted: March 11, 2016
• First Submitted That Met QC Criteria: March 15, 2016
• First Posted (ESTIMATE): March 21, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-384

Drug and device information, study documents

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