An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers

A Phase 3b/4 Safety Trial of Flat Dose Nivolumab In Combination With Ipilimumab in Participants With Non-Small Cell Lung Cancer

A study to evaluate the safety of Nivolumab given in combination with Ipilimumab in patients with advanced cancers. The initial group will enroll patients with newly diagnosed Stage 4 or non-small cell lung cancer that has come back.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Nivolumab in combination with Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 1041
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1199
    • Local Institution - 0007
  • Cordoba, Argentina, 5000
    • Local Institution - 0009
  • Tucuman, Argentina, 4000
    • Local Institution - 0126
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1426
      • Local Institution - 0008
  • RIO Negro
    • Viedma, RIO Negro, Argentina, 8500
      • Local Institution - 0006
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 0038
  • Liege, Belgium, 4000
    • Local Institution - 0037
  • Sint-Niklaas, Belgium, 9100
    • Local Institution - 0036
• Brazil
  • RIO Grande DO SUL
    • Ijui, RIO Grande DO SUL, Brazil, 98700-000
      • Local Institution - 0152
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90610000
      • Local Institution - 0154
    • Porto Alegre, RIO Grande DO SUL, Brazil, 91350-200
      • Local Institution - 0153
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14780-070
      • Local Institution - 0151
• Canada
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Local Institution - 0127
    • Montreal, Quebec, Canada, H4J 1C5
      • Local Institution - 0109
    • Rimouski, Quebec, Canada, G5L 5T1
      • Local Institution - 0049
    • Trois-Rivieres, Quebec, Canada, G8Z 3R9
      • Local Institution - 0050
• Chile
  • Santiago, Chile
    • Local Institution - 0011
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8420383
      • Local Institution - 0010
• Czechia
  • Novy Jicin, Czechia, 741 01
    • Local Institution - 0133
  • Praha 2, Czechia, 128 08
    • Local Institution - 0130
• France
  • Bordeaux, France, 33076
    • Local Institution - 0118
  • Dijon Cedex, France, 21079
    • Local Institution - 0075
  • Marseille Cedex 20, France, 13915
    • Local Institution - 0069
  • Paris, France, 75018
    • Local Institution - 0076
  • Pessac cedex, France, 33604
    • Local Institution - 0074
  • Rennes Cedex 9, France, 35033
    • Local Institution - 0071
  • Saint Herblain, France, 44805
    • Local Institution - 0070
  • Strasbourg Cedex, France, 67091
    • Local Institution - 0072
  • Toulon Cedex, France, 83056
    • Local Institution - 0073
• Germany
  • Frankfurt, Germany, 60488
    • Local Institution - 0023
  • Gera, Germany, 07548
    • Local Institution - 0028
  • Kassel, Germany, 34125
    • Local Institution - 0029
  • Loewenstein, Germany, 74245
    • Local Institution - 0026
  • Wiesbaden, Germany, 65199
    • Local Institution - 0025
• Greece
  • Athens, Greece, 11527
    • Local Institution - 0030
  • N. Faliro, Greece, 18547
    • Local Institution - 0031
  • Thessaloniki, Greece, 56429
    • Local Institution - 0032
• Hungary
  • Budapest, Hungary, 1083
    • Local Institution - 0014
  • Heves
    • Gyöngyös - Mátraháza, Heves, Hungary, 3233
      • Local Institution - 0013
• Italy
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino
  • Meldola, Italy, 47014
    • IRST Meldola
  • Napoli, Italy, 80131
    • Local Institution
  • Napoli, Italy, 80131
    • AOU della Campania Luigi Vanvitelli
  • Rimini, Italy, 47923
    • Ospedale degli Infermi
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
  • Terni, Italy, 05100
    • Azienda Ospedaliera Santa Maria Terni
  • Lombardia
    • Milan, Lombardia, Italy, 20141
      • Local Institution - 0054
• Mexico
  • Monterrey, NL, Mexico, 64060
    • Local Institution - 0019
• Netherlands
  • Groningen, Netherlands, 9714 CZ
    • Local Institution - 0045
  • Rotterdam, Netherlands, 3014 GD
    • Local Institution - 0035
• Poland
  • Bydgoszcz, Poland, 85-796
    • Local Institution - 0015
  • Sucha Beskidzka, Poland, 34-200
    • Local Institution - 0068
  • Warszawa, Poland, 02-781
    • Local Institution - 0016
• Romania
  • Bucuresti, Romania, 021389
    • Local Institution - 0128
  • Craiova, Romania, 200347
    • Local Institution - 0119
  • Romania, Romania, 400015
    • Local Institution - 0120
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Local Institution - 0022
  • Moscow, Russian Federation, 121309
    • Local Institution - 0021
  • St Petersburg, Russian Federation, 198255
    • Local Institution - 0020
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 0061
  • Barcelona, Spain, 08035
    • Local Institution - 0060
  • Jaen, Spain, 23007
    • Local Institution - 0062
  • Madrid, Spain, 28041
    • Local Institution - 0065
  • Majadahonda - Madrid, Spain, 28222
    • Local Institution - 0064
  • Sevilla, Spain, 41013
    • Local Institution - 0063
  • Valencia, Spain, 46026
    • Local Institution - 0059
  • Zaragoza, Spain, 50009
    • Local Institution - 0112
• Switzerland
  • Basel, Switzerland, 4031
    • Local Institution - 0048
  • Zuerich, Switzerland, 8091
    • Local Institution - 0046
• Turkey
  • Antalya, Turkey, 07070
    • Local Institution - 0104
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Local Institution - 0043
  • Wirral, United Kingdom, CH63 4JY
    • Local Institution - 0042
  • Greater London
    • London, Greater London, United Kingdom, SE1 9RT
      • Local Institution - 0041
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Local Institution - 0039
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • Local Institution - 0040
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Local Institution - 0121
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Local Institution - 0148
    • Tucson, Arizona, United States, 85704
      • Local Institution - 0085
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Local Institution - 0164
  • California
    • Bakersfield, California, United States, 93309
      • Local Institution - 0146
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care, Inc
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology/Oncology Medical Group
    • Los Angeles, California, United States, 90095
      • Local Institution - 0115
    • Redondo Beach, California, United States, 90277
      • Torrance Health Association
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System
    • San Luis Obispo, California, United States, 93401
      • Local Institution - 0143
    • Santa Maria, California, United States, 93454
      • Local Institution - 0144
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Whittier, California, United States, 90603
      • Local Institution - 0161
  • Colorado
    • Denver, Colorado, United States, 80218
      • Local Institution - 0083
    • Grand Junction, Colorado, United States, 81501
      • Local Institution - 0141
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Cancer Specialists of North FL
    • Ocala, Florida, United States, 34474
      • Local Institution - 0082
    • Pembroke Pines, Florida, United States, 33028
      • Local Institution - 0147
  • Georgia
    • Athens, Georgia, United States, 30607
      • Local Institution - 0163
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0002
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 0166
  • Illinois
    • Niles, Illinois, United States, 60714
      • Local Institution - 0088
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Local Institution - 0108
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Kentucky One Health St. Joseph East Cancer Center
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Local Institution - 0091
  • Minnesota
    • Edina, Minnesota, United States, 55435-2150
      • Local Institution - 0089
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates, PLLC
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Local Institution - 0077
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Local Institution - 0087
    • Reno, Nevada, United States, 89511
      • Local Institution - 0170
  • New Jersey
    • Belleville, New Jersey, United States, 07109
      • Local Institution - 0156
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
    • Livingston, New Jersey, United States, 07039
      • Local Institution - 0142
  • New York
    • Bronx, New York, United States, 10461
      • Local Institution - 0167
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0004
    • Winston-Salem, North Carolina, United States, 27157
      • Local Institution - 0012
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Local Institution - 0100
    • Cleveland, Ohio, United States, 44109
      • Local Institution - 0134
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Local Institution - 0172
    • Eugene, Oregon, United States, 97401
      • Local Institution - 0096
    • Portland, Oregon, United States, 97239
      • Local Institution - 0176
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0139
    • Pittsburgh, Pennsylvania, United States, 15224
      • Allegheny Health Network
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0159
    • Sayre, Pennsylvania, United States, 18840
      • Local Institution - 0001
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Local Institution - 0123
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Local Institution - 0066
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0067
  • Texas
    • Austin, Texas, United States, 78745
      • Local Institution - 0090
    • Dallas, Texas, United States, 75230
      • Texas Oncology, P.A.
    • Dallas, Texas, United States, 75231
      • Local Institution - 0149
    • Fort Worth, Texas, United States, 76104
      • Local Institution - 0094
    • Longview, Texas, United States, 75601
      • Local Institution - 0093
    • Plano, Texas, United States, 75075-7787
      • Local Institution - 0098
    • Waco, Texas, United States, 76712
      • Local Institution - 0086
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 0097
    • Richmond, Virginia, United States, 23230
      • Local Institution - 0044
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Renton, Washington, United States, 98055
      • Local Institution - 0174
    • Spokane, Washington, United States, 99208
      • Local Institution - 0173

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed Stage 4 or recurrent non-small cell lung cancer
• Eastern Cooperative Oncology Group (ECOG) score 0-1 (Physically able to carry out light housework or office work through to being fully active as you were before cancer)
• No prior systemic anticancer therapy (including EGFR and ALK inhibitors)
• Tissue or Programmed death-ligand 1 (PD-L1) results available

Cohort 1A Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) score 2 or
• Eastern Cooperative Oncology Group (ECOG) score 0-1 and one disease specific criteria as listed in the protocol

Cohort C Inclusion Criteria:

• High Tumor Mutation Burden

Exclusion Criteria:

• Untreated brain metastases
• An active malignancy that requires concurrent intervention
• Active, known or suspected autoimmune disease
• Carcinomatous meningitis, which means there is inflammation of the covering of the brain, caused by cancer

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab in combination with Ipilimumab; Specified dose on specified days	Drug: Nivolumab in combination with Ipilimumab; Specified dose on specified days; Other Names: BMS-936558 (Nivolumab); Opdivo (Nivolumab); BMS-734016 (Ipilimumab); Yervoy (Ipilimumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs)	Drug related AEs are those events with relationship to study drug. If the relationship to study drug is missing, the AE will be considered as drug-related. The select AEs of interest are the following: Pulmonary, Renal, Gastrointestinal, Hepatic, Skin, Endocrine, and hypersensitivity/infusion reaction events. AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death	From first dose to 30 days post last dose (Up to approximately 27 months)
Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs)	imAEs are specific events that include pneumonitis, diarrhea/colitis, hepatitis, nephritis/renal dysfunction, rash, and endocrine (adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis). AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death	From first dose to 100 days post last dose (Up to approximately 29 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression.	From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months)
Overall Survival (OS)	OS is defined as the time from first dosing date to the date of death. A participant who has not died will be censored at last known date alive.	From first dosing date to the date of death (Up to approximately 67 months)
Objective Response Rate (ORR)	ORR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR). CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From first dosing date up to approximately 67 months
Duration of Response (DoR)	DoR is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression per RECIST 1.1, or death due to any cause, whichever occurs first. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression.	From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months)
Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L)	FACT-L is a quality-of-life questionnaire which includes Lung Cancer Subscale (LCS) that assesses the treatment impact on lung cancer related symptoms in 5 domains: Physical, social/family, emotional, and functional well-being using a 5-point scale (0=not at all; 1=a little bit, 2=somewhat; 3=quite a bit; 4=very much) added to obtain total score. The ranges of possible total scores are 0-136 for the FACT-L with a higher score representing better quality of life, improved symptomatology and enhanced physical/functional outcomes. According to Functional Assessment of Chronic Illness Therapy scoring guidelines, in the event of missing responses for some of the questions, scores will be prorated using the average of the other answers in that scale. Baseline is defined as events that occur before the date/time of first dose. Post treatment visits include follow-up (FU) visit 1, FU visit 2, and subsequent survival FU visits to occur every 3 months up until survival FU visit 18.	From baseline and up to subsequent survival follow-up visit 18 (Up to approximately 67 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2016
• Primary Completion (Actual): May 13, 2022
• Study Completion (Actual): May 13, 2022

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (Estimated): August 17, 2016

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 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; Ipilimumab
• Other Study ID Numbers: CA209-817; 2016-002621-10 (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