A Randomized Phase II Study of Tepotinib With or Without Ramucirumab in Participants With MET Exon 14 Skipping Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP SUB-STUDY)
Summary
This phase II Expanded Lung-MAP treatment trial tests tepotinib with or without ramucirumab for the treatment of patients with advanced non-small cell lung cancer that has spread from where it first started (primary site) to other places in the body (stage IV) or that has come back after a period of improvement (recurrent). Tepotinib is used in patients whose cancer has a mutated (changed) form of a gene called MET. It is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal MET protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving tepotinib with ramucirumab may lower the chance of the cancer from growing or spreading in patients with stage IV or recurrent non-small cell lung cancer.
Detailed description
PRIMARY OBJECTIVE: I. To compare the response rate (confirmed or unconfirmed, complete or partial) between participants with MET exon 14 skipping positive non-small cell lung cancer (NSCLC) randomized to tepotinib with or without ramucirumab. SECONDARY OBJECTIVES: I. To compare the frequency of all-grade treatment- related peripheral edema as defined by Common Terminology Criteria for Adverse Events (CTCAE) between the arms. II. To evaluate the frequency and severity of toxicities within each arm. III. To compare progression-free survival between the arms. IV. To compare overall survival between the arms. V. To estimate the duration of response (DoR) among responders within each arm. TRANSLATIONAL MEDICINE OBJECTIVE: I. To establish a tissue/blood repository for participants with MET exon 14 skipping non-small cell lung cancer (NSCLC). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on day 1 of each cycle and tepotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients optionally undergo lymphoscintigraphy scan at screening prior to treatment, at the first occurrence of peripheral edema (defined as the development of grade ≥ 1 CTCAE Edema Limbs affecting either the arms, hands, or legs), and if peripheral edema increases in attribution. Patients also undergo blood collection, computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Additionally, patients undergo urine collection during screening and on study. After completion of study treatment, patients are followed-up every 12 weeks or more often as clinically indicated until progression and then every 6 months for 2 years and at the end of 3 years from date of sub-study randomization.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo blood and urine sample collection
- ProcedureComputed Tomography
Undergo CT scan
- ProcedureLymphoscintigraphy
Undergo lymphoscintigraphy scan
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- BiologicalRamucirumab
Given IV
- DrugTepotinib
Given PO
Outcome measures
Primary
Response rate
Rates will be compared using a chi-squared test at the 1-sided 10% level and also presented as the difference in response rates with the associated 80% confidence interval for the difference, Further, response rates and associated 80% confidence interval will be estimated for each arm.
Time frame: Up to 3 years from date of sub-study randomization
Secondary
Incidence of treatment-related peripheral edema
Time frame: Up to 3 years from date of sub-study randomization
Incidence and severity of toxicities
Time frame: Up to 3 years from date of sub-study randomization
Progression-free survival
Time frame: From date of sub-study randomization to date of first documentation of progression or death due to any cause, assessed up to 3 years
Overall survival
Time frame: Up to 3 years from date of sub-study randomization
Duration of response
Time frame: From date of first documentation of response (complete response [CR] or partial response [PR]) to date of first documentation of progression or death due to any cause among participants who achieve a response (CR or PR), assessed up to 3 years
Eligibility criteria
Study locations (266)
Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
Daphne, Alabama, 36526
Thomas Hospital
Fairhope, Alabama, 36532
Mobile Infirmary Medical Center
Mobile, Alabama, 36607
Gulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
Saraland, Alabama, 36571
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, 72401
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Kaiser Permanente-Anaheim
Anaheim, California, 92806
Sutter Auburn Faith Hospital
Auburn, California, 95602
Kaiser Permanente-Baldwin Park
Baldwin Park, California, 91706
Kaiser Permanente-Bellflower
Bellflower, California, 90706
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Kaiser Permanente-Fontana
Fontana, California, 92335
Palo Alto Medical Foundation-Fremont
Fremont, California, 94538
Kaiser Permanente South Bay
Harbor City, California, 90710
Kaiser Permanente-Irvine
Irvine, California, 92618
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Kaiser Permanente West Los Angeles
Los Angeles, California, 90034
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Memorial Medical Center
Modesto, California, 95355
Kaiser Permanente-Ontario
Ontario, California, 91761
Palo Alto Medical Foundation Health Care
Palo Alto, California, 94301
Kaiser Permanente - Panorama City
Panorama City, California, 91402
Eisenhower Medical Center
Rancho Mirage, California, 92270
Kaiser Permanente-Riverside
Riverside, California, 92505
Sutter Roseville Medical Center
Roseville, California, 95661
Sutter Medical Center Sacramento
Sacramento, California, 95816
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Kaiser Permanente-San Diego Zion
San Diego, California, 92120
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115
Kaiser Permanente-San Francisco
San Francisco, California, 94115
Kaiser Permanente-San Marcos
San Marcos, California, 92078
Mills Health Center
San Mateo, California, 94401
Palo Alto Medical Foundation-Santa Cruz
Santa Cruz, California, 95065
Sutter Pacific Medical Foundation
Santa Rosa, California, 95403
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, 94086
Cedars-Sinai Cancer - Tarzana
Tarzana, California, 91356
Torrance Memorial Physician Network - Cancer Care
Torrance, California, 90505
Kaiser Permanente-Vallejo
Vallejo, California, 94589
Sutter Solano Medical Center/Cancer Center
Vallejo, California, 94589
Kaiser Permanente-Woodland Hills
Woodland Hills, California, 91367
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Medical Center of the Rockies
Loveland, Colorado, 80538
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, 06033
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105
Yale University
New Haven, Connecticut, 06520
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, 06902
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385
Bayhealth Hospital Kent Campus
Dover, Delaware, 19901
Bayhealth Hospital Sussex Campus
Milford, Delaware, 19963
Kaiser Permanente-Capitol Hill Medical Center
Washington D.C., District of Columbia, 20002
Moffitt Cancer Center
Tampa, Florida, 33612
University Cancer and Blood Center LLC
Athens, Georgia, 30607
Northeast Georgia Medical Center-Gainesville
Gainesville, Georgia, 30501
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Illinois CancerCare-Canton
Canton, Illinois, 61520
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Northwestern University
Chicago, Illinois, 60611
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
Carle at The Riverfront
Danville, Illinois, 61832
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Edward Hines Jr VA Hospital
Hines, Illinois, 60141
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Loyola University Medical Center
Maywood, Illinois, 60153
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Northwestern Medicine Oak Brook
Oak Brook, Illinois, 60523
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Illinois CancerCare-Peru
Peru, Illinois, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Memorial Hospital East
Shiloh, Illinois, 62269
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Carle Cancer Center
Urbana, Illinois, 61801
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Illinois CancerCare - Washington
Washington, Illinois, 61571
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
McFarland Clinic - Boone
Boone, Iowa, 50036
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
HaysMed
Hays, Kansas, 67601
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Salina Regional Health Center
Salina, Kansas, 67401
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
Kaiser Permanente-Woodlawn Medical Center
Baltimore, Maryland, 21244
Kaiser Permanente-Gaithersburg Medical Center
Gaithersburg, Maryland, 20879
Kaiser Permanente - Largo Medical Center
Largo, Maryland, 20774
Kaiser Permanente Lutherville - Timonium Medical Center
Lutherville, Maryland, 21093
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
MyMichigan Medical Center Saginaw
Saginaw, Michigan, 48601
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, 48604
MyMichigan Medical Center Tawas
Tawas City, Michigan, 48764
Saint Mary's Oncology/Hematology Associates of West Branch
West Branch, Michigan, 48661
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
Essentia Health Sandstone
Sandstone, Minnesota, 55072
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Baptist Memorial Hospital and Cancer Center-Union County
New Albany, Mississippi, 38652
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
University Health Truman Medical Center
Kansas City, Missouri, 64108
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, 64086
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital South
St Louis, Missouri, 63128
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Community Hospital of Anaconda
Anaconda, Montana, 59711
Billings Clinic Cancer Center
Billings, Montana, 59101
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Logan Health Medical Center
Kalispell, Montana, 59901
Community Medical Center
Missoula, Montana, 59804
OptumCare Cancer Care at Charleston
Las Vegas, Nevada, 89102
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89183
New Hampshire Oncology Hematology PA-Concord
Concord, New Hampshire, 03301
Solinsky Center for Cancer Care
Manchester, New Hampshire, 03103
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Virtua Samson Cancer Center
Moorestown, New Jersey, 08057
Virtua Voorhees
Voorhees Township, New Jersey, 08043
Memorial Sloan Kettering Commack
Commack, New York, 11725
Mary Imogene Bassett Hospital
Cooperstown, New York, 13326
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Rochester
Rochester, New York, 14642
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
FirstHealth of the Carolinas-Moore Regional Hospital
Pinehurst, North Carolina, 28374
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Aultman Health Foundation
Canton, Ohio, 44710
Miami Valley Hospital South
Centerville, Ohio, 45459
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Miami Valley Hospital
Dayton, Ohio, 45409
Premier Blood and Cancer Center
Dayton, Ohio, 45409
Miami Valley Hospital North
Dayton, Ohio, 45415
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331
ProMedica Flower Hospital
Sylvania, Ohio, 43560
Upper Valley Medical Center
Troy, Ohio, 45373
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Providence Newberg Medical Center
Newberg, Oregon, 97132
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Kaiser Permanente Northwest
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
WellSpan Medical Oncology and Hematology
Chambersburg, Pennsylvania, 17201
Geisinger Medical Center
Danville, Pennsylvania, 17822
Geisinger Cancer Center Dickson City
Dickson City, Pennsylvania, 18519
Ephrata Cancer Center
Ephrata, Pennsylvania, 17522
Adams Cancer Center
Gettysburg, Pennsylvania, 17325
Sechler Family Cancer Center
Lebanon, Pennsylvania, 17042
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837
Community Medical Center
Scranton, Pennsylvania, 18510
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Cancer Care Associates of York
York, Pennsylvania, 17403
WellSpan Health-York Cancer Center
York, Pennsylvania, 17403
WellSpan Health-York Hospital
York, Pennsylvania, 17403
AnMed Health Cancer Center
Anderson, South Carolina, 29621
Medical University of South Carolina
Charleston, South Carolina, 29425
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
The Don and Sybil Harrington Cancer Center
Amarillo, Texas, 79106
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Kaiser Permanente Tysons Corner Medical Center
McLean, Virginia, 22102
Kaiser Permanente-Caton Hill Medical Center
Woodbridge, Virginia, 22192
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
Swedish Medical Center-First Hill
Seattle, Washington, 98122
Edwards Comprehensive Cancer Center
Huntington, West Virginia, 25701
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476