Testing the Addition of Radiation Therapy to the Usual Treatment (Immunotherapy With or Without Chemotherapy) for Advanced Stage Non-small Cell Lung Cancer Patients Who Are PD-L1 Negative

May 12, 2026 updated by: National Cancer Institute (NCI)

A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy With or Without Radiation Therapy for PD-L1-Negative, Advanced Non-Small Cell Lung Cancer

This phase II/III trial compares the addition of radiation therapy to the usual treatment (immunotherapy with or without chemotherapy) versus (vs.) usual treatment alone in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) whose tumor is also negative for a molecular marker called PD-L1. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The addition of radiation therapy to usual treatment may stop the cancer from growing and increase the life of patients with advanced non-small cell lung cancer who are PD-L1 negative.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To assess if radiation improves the progression free survival (PFS, phase II portion) and overall survival (OS, phase III portion) of advanced stage non-small cell lung cancer (NSCLC) patients with PD-L1 tumor proportion score (TPS) < 1% who receive immunotherapy with or without chemotherapy.

SECONDARY OBJECTIVES:

I. To estimate and compare the rates of >= grade 3-4 and all grade adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 between the arms.

II. To summarize and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) between the arms.

III. To determine and compare the objective response rate (ORR) per RECIST between the arms (including at both irradiated and un-irradiated sites).

QUALITY OF LIFE (QOL) OBJECTIVE:

I. To assess the health-related QOL in both treatment arms.

CORRELATIVE SCIENCE OBJECTIVE:

I. To evaluate changes in the peripheral immune microenvironment between the arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity or patients may receive standard of care systemic immunotherapy. Patients also undergo magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as echocardiography (ECHO) during screening.

Arm B: Patients receive nivolumab IV over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity or patients may receive standard of care systemic immunotherapy. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for years 4-5 following randomization until disease progression. Following disease progression patients are followed for survival every 6 months for up to 5 years following randomization.

Study Type

Interventional

Enrollment (Estimated)

427

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital in Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Medical Center-Herrick Campus
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Irvine, California, United States, 92618
        • City of Hope at Irvine Lennar
      • Lancaster, California, United States, 93534
        • City of Hope Antelope Valley
      • Marysville, California, United States, 95901
        • Fremont - Rideout Cancer Center
      • Modesto, California, United States, 95355
        • Memorial Medical Center
      • Napa, California, United States, 94558
        • Providence Queen of The Valley
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • South Pasadena, California, United States, 91030
        • City of Hope South Pasadena
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Upland, California, United States, 91786
        • City of Hope Upland
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Fort Collins, Colorado, United States, 80528
        • Cancer Care and Hematology-Fort Collins
      • Greeley, Colorado, United States, 80631
        • UCHealth Greeley Hospital
      • Loveland, Colorado, United States, 80538
        • Medical Center of the Rockies
    • Delaware
      • Millville, Delaware, United States, 19967
        • Beebe South Coastal Health Campus
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
      • Newark, Delaware, United States, 19713
        • Medical Oncology Hematology Consultants PA
      • Rehoboth Beach, Delaware, United States, 19971
        • Beebe Health Campus
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • MedStar Washington Hospital Center
    • Florida
      • Aventura, Florida, United States, 33180
        • UM Sylvester Comprehensive Cancer Center at Aventura
      • Clearwater, Florida, United States, 33756
        • Morton Plant Hospital
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • UM Sylvester Comprehensive Cancer Center at Kendall
      • Plantation, Florida, United States, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
      • Winter Haven, Florida, United States, 33881
        • Winter Haven Hospital
    • Georgia
      • Newnan, Georgia, United States, 30265
        • CTCA at Southeastern Regional Medical Center
      • Savannah, Georgia, United States, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Fruitland, Idaho, United States, 83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83687
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • DeKalb, Illinois, United States, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Glenview, Illinois, United States, 60026
        • Northwestern Medicine Glenview Outpatient Center
      • Grayslake, Illinois, United States, 60030
        • Northwestern Medicine Grayslake Outpatient Center
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Lake Forest, Illinois, United States, 60045
        • Northwestern Medicine Lake Forest Hospital
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • O'Fallon, Illinois, United States, 62269
        • HSHS Saint Elizabeth's Hospital
      • Orland Park, Illinois, United States, 60462
        • University of Chicago Medicine-Orland Park
      • Rockford, Illinois, United States, 61114
        • UW Health Carbone Cancer Center Rockford
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Springfield, Illinois, United States, 62781
        • Springfield Memorial Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Indiana
      • Crown Point, Indiana, United States, 46307
        • UChicago Medicine Northwest Indiana
    • Iowa
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Ames, Iowa, United States, 50010
        • McFarland Clinic - Ames
      • Ankeny, Iowa, United States, 50023
        • UI Health Care Mission Cancer and Blood - Ankeny Clinic
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Clive, Iowa, United States, 50325
        • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
      • Creston, Iowa, United States, 50801
        • Greater Regional Medical Center
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50309
        • UI Health Care Mission Cancer and Blood - Des Moines Clinic
      • Des Moines, Iowa, United States, 50314
        • UI Health Care Mission Cancer and Blood - Laurel Clinic
      • Waukee, Iowa, United States, 50263
        • UI Health Care Mission Cancer and Blood - Waukee Clinic
      • West Des Moines, Iowa, United States, 50266
        • Mercy Medical Center-West Lakes
      • West Des Moines, Iowa, United States, 50266
        • The Iowa Clinic PC
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Lexington, Kentucky, United States, 40509
        • Saint Joseph Hospital East
    • Maine
      • Sanford, Maine, United States, 04073
        • MaineHealth Cancer Care Center of York County
      • Scarborough, Maine, United States, 04074
        • MaineHealth Maine Medical Center- Scarborough
      • South Portland, Maine, United States, 04106
        • MaineHealth Cancer Care and IV Therapy - South Portland
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
      • Brighton, Michigan, United States, 48114
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
      • Brighton, Michigan, United States, 48114
        • Trinity Health Medical Center - Brighton
      • Canton, Michigan, United States, 48188
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
      • Canton, Michigan, United States, 48188
        • Trinity Health Medical Center - Canton
      • Chelsea, Michigan, United States, 48118
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
      • Chelsea, Michigan, United States, 48118
        • Chelsea Hospital
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Lansing, Michigan, United States, 48912
        • University of Michigan Health - Sparrow Lansing
      • Livonia, Michigan, United States, 48154
        • Trinity Health Saint Mary Mercy Livonia Hospital
      • Pontiac, Michigan, United States, 48341
        • Trinity Health Saint Joseph Mercy Oakland Hospital
      • Pontiac, Michigan, United States, 48341
        • Michigan Healthcare Professionals Pontiac
      • Saginaw, Michigan, United States, 48604
        • Oncology Hematology Associates of Saginaw Valley PC
      • Saginaw, Michigan, United States, 48601
        • MyMichigan Medical Center Saginaw
      • Tawas City, Michigan, United States, 48764
        • MyMichigan Medical Center Tawas
      • West Branch, Michigan, United States, 48661
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48197
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Miller-Dwan Hospital
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Robbinsdale, Minnesota, United States, 55422
        • North Memorial Medical Health Center
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Rolla, Missouri, United States, 65401
        • Phelps Health Delbert Day Cancer Institute
      • Sainte Genevieve, Missouri, United States, 63670
        • Sainte Genevieve County Memorial Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
      • St Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • St Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • St Louis, Missouri, United States, 63128
        • Mercy Hospital South
      • Sullivan, Missouri, United States, 63080
        • Missouri Baptist Sullivan Hospital
      • Sunset Hills, Missouri, United States, 63127
        • BJC Outpatient Center at Sunset Hills
    • Montana
      • Bozeman, Montana, United States, 59715
        • Bozeman Health Deaconess Hospital
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • New York, New York, United States, 10019
        • Mount Sinai West
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10011
        • Mount Sinai Chelsea
      • New York, New York, United States, 10075
        • Lenox Hill Hospital
      • New York, New York, United States, 10065
        • Manhattan Eye Ear and Throat Hospital
      • Oswego, New York, United States, 13126
        • Upstate Cancer Center at Oswego
      • Oswego, New York, United States, 13126
        • Upstate Cancer Center Radiation Oncology at Oswego
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • Syracuse, New York, United States, 13215
        • SUNY Upstate Medical Center-Community Campus
      • Syracuse, New York, United States, 13210
        • Upstate Cancer Center at Hill Radiation Oncology
      • Verona, New York, United States, 13478
        • Upstate Cancer Center at Verona
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Raleigh, North Carolina, United States, 27609
        • Duke Cancer Center Raleigh
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health System - Akron Campus
    • Oklahoma
      • Lawton, Oklahoma, United States, 73505
        • Cancer Centers of Southwest Oklahoma Research
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73120
        • Mercy Hospital Oklahoma City
    • Oregon
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Tualatin, Oregon, United States, 97062
        • Legacy Meridian Park Hospital
    • Pennsylvania
      • Chadds Ford, Pennsylvania, United States, 19317
        • Christiana Care Health System-Concord Health Center
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Lewisburg, Pennsylvania, United States, 17837
        • Geisinger Medical Oncology-Lewisburg
      • Reading, Pennsylvania, United States, 19605
        • Penn State Health Saint Joseph Medical Center
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Amarillo, Texas, United States, 79106
        • The Don and Sybil Harrington Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23235
        • VCU Massey Cancer Center at Stony Point
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
      • Tappahannock, Virginia, United States, 22560
        • VCU Health Tappahannock Hospital
    • Washington
      • Vancouver, Washington, United States, 98686
        • Legacy Salmon Creek Hospital
      • Vancouver, Washington, United States, 98684
        • Legacy Cancer Institute Medical Oncology and Day Treatment
      • Walla Walla, Washington, United States, 99362
        • Providence Saint Mary Regional Cancer Center
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston Division
    • Wisconsin
      • Ashland, Wisconsin, United States, 54806
        • Northwest Wisconsin Cancer Center
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Medical Center-EC Cancer Center
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • La Crosse, Wisconsin, United States, 54601
        • Mayo Clinic Health System-Franciscan Healthcare
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Minocqua, Wisconsin, United States, 54548
        • Marshfield Medical Center - Minocqua
      • Mukwonago, Wisconsin, United States, 53149
        • ProHealth D N Greenwald Center
      • New Richmond, Wisconsin, United States, 54017
        • Cancer Center of Western Wisconsin
      • Oconomowoc, Wisconsin, United States, 53066
        • ProHealth Oconomowoc Memorial Hospital
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Waukesha, Wisconsin, United States, 53188
        • UW Cancer Center at ProHealth Care
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologic or cytologic diagnosis of stage IV NSCLC using version American Joint Committee on Cancer (AJCC) 8th edition (includes M1a, M1b, and M1c stage disease). Patients with stage IIIB and IIIC disease are eligible if they are not a candidate for combined chemotherapy and radiation
  • PD-L1 expression tumor proportion score (TPS) < 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed patients are not eligible. The assay must have been performed locally by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory. The type of assay will be recorded
  • For non-squamous patients only (adenocarcinoma or adenosquamous): EGFR, ALK and ROS1 testing must be done locally. No patients with known actionable EGFR mutations (except exon 20 insertion), ALK or ROS1 mutations that can be treated with oral tyrosine inhibitors
  • Measurable disease based on RECIST 1.1, including at least two cancerous deposits. At least one deposit must be RECIST measurable (and not to be irradiated) while at least one OTHER deposit (measurable or non-measurable) must meet criteria for three 8 gray (Gy) doses of radiation
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • No more than three weeks of treatment with systemic chemotherapy or immunotherapy for advanced NSCLC
  • No more than three weeks of treatment with checkpoint inhibitors for metastatic lung cancer
  • No treatment with chemotherapy or immunotherapy for non-metastatic disease (e.g., adjuvant therapy) within 6 months prior to registration
  • No systemic immunostimulatory or immunosuppressive drugs, including > 10 mg prednisone equivalent per day, within 2 weeks or 5 half-live of the drug, whichever is shorter. Steroid premedication per local standard is allowed
  • >= 1 week prior to registration since palliative (including central nervous system [CNS]) radiotherapy to any tumor site
  • No prior allogeneic tissue/solid organ transplant
  • No uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
  • No current pneumonitis or history of non-infectious pneumonitis that required steroids
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration
  • No active auto-immune disease that requires systemic therapy within 2 years prior to registration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
  • No patients with symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with small asymptomatic brain metastases are eligible as are patients with treated brain metastases that require no steroids
  • Not pregnant and not nursing, because this study involves radiation as well as potentially chemotherapy which have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
  • No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 2 years. Participants with non-melanoma skin cancers or carcinoma in-situ (e.g., breast carcinoma, urothelial carcinoma or cervical cancer in situ) or localized prostate cancer (T1-3, N0, M0) that have undergone potentially curative therapy are eligible
  • No hypersensitivity (>= grade 3) to immunotherapy and/or any of its excipients
  • No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,FluMist [registered trademark]) are live attenuated vaccines and are not allowed. COVID-19 vaccine is allowed
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated (Calc.) creatinine clearance >= 45 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (immunotherapy, +/- chemotherapy)
Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity or patients may receive standard of care systemic immunotherapy. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • MDX 1106
  • MDX1106
  • BMS 936558
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
  • BMS936558
  • ONO 4538
  • ONO4538
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy
  • MDX010
  • BMS734016
  • BMS 734016
  • MDX 010
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Echocardiography Test
Undergo ECHO
Other Names:
  • Echocardiography
  • EC
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy
Experimental: Arm B (immunotherapy, +/- chemotherapy, radiation therapy)
Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • MDX 1106
  • MDX1106
  • BMS 936558
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
  • BMS936558
  • ONO 4538
  • ONO4538
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy
  • MDX010
  • BMS734016
  • BMS 734016
  • MDX 010
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Energy Type
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Echocardiography Test
Undergo ECHO
Other Names:
  • Echocardiography
  • EC
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) (Phase II)
Time Frame: From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years
Will be performed on an intent-to-treat (ITT) basis.
From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years
Overall survival (OS) (Phase III)
Time Frame: From randomization and death of all causes, assessed up to 5 years
Will be performed on an ITT basis. The comparison of the distributions of OS between treatment arms will be done with a one-sided stratified log-rank test). The rates at various time points (e.g., every 6 months after randomization) and medians of OS for each arm will be estimated using the Kaplan-Meier estimator. The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios will be estimated using a stratified Cox regression model. The final phase III analysis of OS will be considered as "positive" if the stratified log-rank test statistics Z-value greater than the critical value adjusted for type 1 error using group sequential methods. Multivariable Cox models will be used to evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, systemic therapy, histology and performance status.
From randomization and death of all causes, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years
Assessed per Response Evaluation Criteria in Solid Tumors (RECIST).
From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years
Quality of life
Time Frame: Up to 5 years
Up to 5 years
Incidence of treatment-related adverse events
Time Frame: Up to 5 years
Treatment-related toxicity will be summarized by grade, type, and system organ class. Comparisons of the percentages of patients experiencing an adverse event between Arm A and Arm B will be performed using Fisher's exact test.
Up to 5 years
Objective response rate (ORR)
Time Frame: Up to 5 years
Assessed per RECIST for both irradiated and un-irradiated areas. The ORRs between treatments will be compared with Fisher's exact test. The difference of ORR between treatments will be estimated by the Miettinen-Nurminen method and its 95% CI will be given. Multivariable logistic regression will be used to evaluate the treatment effect on ORR while adjusting for significant baseline covariates.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Christine M Bestvina, Alliance for Clinical Trials in Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2022

Primary Completion (Estimated)

December 12, 2030

Study Completion (Estimated)

December 12, 2030

Study Registration Dates

First Submitted

June 16, 2021

First Submitted That Met QC Criteria

June 16, 2021

First Posted (Actual)

June 18, 2021

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2021-06042 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • A082002 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lung Adenocarcinoma

Clinical Trials on Nivolumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe