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Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)

RecruitingPhase 2

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)

Who can join

18 Minutes · All sexes

Full eligibility criteria
Inclusion Criteria:

* Participants must have been assigned to S1900K by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900K is determined by the LUNGMAP protocol
* Participants must have documentation of stage IV or recurrent NSCLC with a MET exon 14 skipping mutation determined by tissue-based or blood-based (circulating tumor DNA \[ctDNA\]) next generation sequencing (NGS) assay done within a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO)/ International Electrotechnical Commission (IEC), College of American Pathologists (CAP), or similar certification. Documentation must either be:

  * NGS test results from tissue submitted for LUNGMAP screening, or
  * Submitted documentation in the LUNGMAP Rave Electronic Data Capture System of a MET exon 14 skipping mutation from a previously completed tissue or blood-based NGS test
* Participants must have measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document measurable disease ONLY if it is of diagnostic quality, otherwise, it may be used to document non-measurable disease only. Measurable disease must be assessed within 28 days prior to sub-study randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study randomization. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to sub-study randomization to be considered measurable
* Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study randomization
* Participants must not have leptomeningeal disease, spinal cord compression or brain metastases unless:

  * Metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 3 days following the stereotactic radiation and/or 14 days following whole brain radiation, and prior to sub-study randomization, AND
  * Participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study randomization
* Participants must not have other known actionable oncogenic alterations, such as (but not limited to) EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS1 gene rearrangement, RET gene rearrangement, NTRK rearrangement, HER2 mutation, KRAS activating mutations, and BRAF V600E mutation
* Participants who have received at least one line of systemic treatment for stage IV or recurrent NSCLC must have progressed (in the opinion of the treating physician) following the most recent line of therapy. Participants who have not yet received systemic treatment for their stage IV or recurrent NSCLC are allowed
* Participants may have received any number of lines of therapy for stage IV or recurrent NSCLC (including zero) and must be able to report prior treatment information
* Participants must have recovered (=\< grade 1) from any side effects of prior therapy for NSCLC except alopecia and vitiligo
* Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study randomization
* Participants must not have received treatment with prior MET inhibitor therapies (e.g., crizotinib, tivantinib, savolitinib, tepotinib, cabozantinib, and foretinib).
* Participants must not have received treatment with prior angiogenesis inhibitor therapies (including but not limited to bevacizumab and ramucirumab)
* Participants must not have a history of interstitial lung disease that required steroid treatment
* Participants must not have received any radiation therapy within 7 days prior to sub-study randomization with the exceptions of

  * Stereotactic radiation to CNS metastases which must have been completed at least 3 days prior to sub-study randomization and
  * Palliative radiotherapy to bone metastases which must have been completed at least 1 day prior to sub-study randomization
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
* Participants must not have had a major surgery within 14 days prior to sub-study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to sub-study randomization)
* Hemoglobin \>= 9.0 g/dL (within 28 days prior to sub-study randomization)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to sub-study randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN (within 28 days prior to sub-study randomization)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 × institutional ULN. Participants with history of liver metastasis must have AST and ALT =\< 5 x ULN (within 28 days prior to sub-study randomization)
* Participants must have a serum creatinine =\< the institutional upper limit of normal (IULN) or calculated creatinine clearance \>= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to sub-study randomization
* Participants must have a cystatin C test performed to obtain baseline value within 28 days prior to sub-study randomization
* Participants' most recent Zubrod performance status must be 0-1 and be documented within 28 days prior to sub-study randomization
* Participants must have a completed medical history and physical exam within 28 days prior to sub-study randomization
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy and have undetectable viral load test on the most recent test results obtained within 6 months prior to sub-study randomization
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to sub-study randomization, if indicated by the treating investigator
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to sub-study randomization, if indicated by the treating investigator
* Participants must not have cirrhosis at a level of Child-Pugh B (or worse) OR any degree of cirrhosis AND a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis
* Participants must not have grade \< 0 of peripheral edema within 28 days prior to sub-study randomization
* Participants must not have experienced any arterial thromboembolic events, including but not limited to transient ischemic attack or cerebrovascular accident within 6 months prior to sub-study randomization
* Participants must not have uncontrolled blood pressure and hypertension within 28 days prior to sub-study randomization
* Participants must not be pregnant or breastfeeding (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must also be offered participation in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

  * NOTE: Participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

About the study

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.

What is being tested

Sponsor: SWOG Cancer Research Network · Participants: 56 · Started: Aug 8, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06031688

Locations in the U.S.

AlabamaGulf Health Hospitals Inc/Infirmary Cancer Care - Malbis, Daphne
Thomas Hospital, Fairhope
Mobile Infirmary Medical Center, Mobile
Gulf Health Hospitals Inc/Infirmary Cancer Care - Saraland, Saraland
ArkansasNEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro
University of Arkansas for Medical Sciences, Little Rock
CaliforniaSutter Auburn Faith Hospital, Auburn
Alta Bates Summit Medical Center-Herrick Campus, Berkeley
Tower Cancer Research Foundation, Beverly Hills
Palo Alto Medical Foundation-Fremont, Fremont
UC San Diego Moores Cancer Center, La Jolla
Cedars-Sinai Medical Center, Los Angeles
Memorial Medical Center, Modesto
Eisenhower Medical Center, Rancho Mirage
Sutter Roseville Medical Center, Roseville
Sutter Medical Center Sacramento, Sacramento
University of California Davis Comprehensive Cancer Center, Sacramento
California Pacific Medical Center-Pacific Campus, San Francisco
Kaiser Permanente-San Francisco, San Francisco
Mills Health Center, San Mateo
Palo Alto Medical Foundation-Santa Cruz, Santa Cruz
Sutter Pacific Medical Foundation, Santa Rosa
Palo Alto Medical Foundation-Sunnyvale, Sunnyvale
Cedars-Sinai Cancer - Tarzana, Tarzana
Torrance Memorial Physician Network - Cancer Care, Torrance
Kaiser Permanente-Vallejo, Vallejo
Sutter Solano Medical Center/Cancer Center, Vallejo
ColoradoUCHealth University of Colorado Hospital, Aurora
Memorial Hospital North, Colorado Springs
UCHealth Memorial Hospital Central, Colorado Springs
Cancer Care and Hematology-Fort Collins, Fort Collins
Poudre Valley Hospital, Fort Collins
UCHealth Greeley Hospital, Greeley
Medical Center of the Rockies, Loveland
ConnecticutSmilow Cancer Hospital-Derby Care Center, Derby
Smilow Cancer Hospital Care Center-Fairfield, Fairfield
Smilow Cancer Hospital Care Center at Glastonbury, Glastonbury
Smilow Cancer Hospital Care Center at Greenwich, Greenwich
Smilow Cancer Hospital Care Center - Guilford, Guilford
Smilow Cancer Hospital Care Center at Saint Francis, Hartford
Yale University, New Haven
Yale-New Haven Hospital North Haven Medical Center, North Haven
Smilow Cancer Hospital Care Center at Long Ridge, Stamford
Smilow Cancer Hospital-Torrington Care Center, Torrington
Smilow Cancer Hospital Care Center-Trumbull, Trumbull
Smilow Cancer Hospital-Waterbury Care Center, Waterbury
Smilow Cancer Hospital Care Center - Waterford, Waterford
DelawareBayhealth Hospital Kent Campus, Dover
Bayhealth Hospital Sussex Campus, Milford
District of ColumbiaKaiser Permanente-Capitol Hill Medical Center, Washington D.C.
FloridaMoffitt Cancer Center, Tampa
GeorgiaUniversity Cancer and Blood Center LLC, Athens
Northeast Georgia Medical Center-Gainesville, Gainesville
IdahoSaint Alphonsus Cancer Care Center-Boise, Boise
Saint Alphonsus Cancer Care Center-Caldwell, Caldwell
Kootenai Health - Coeur d'Alene, Coeur d'Alene
Saint Alphonsus Cancer Care Center-Nampa, Nampa
Kootenai Clinic Cancer Services - Post Falls, Post Falls
Kootenai Clinic Cancer Services - Sandpoint, Sandpoint
IllinoisIllinois CancerCare-Bloomington, Bloomington
Illinois CancerCare-Canton, Canton
Illinois CancerCare-Carthage, Carthage
John H Stroger Jr Hospital of Cook County, Chicago
Northwestern University, Chicago
Carle at The Riverfront, Danville
Northwestern Medicine Cancer Center Kishwaukee, DeKalb
Cancer Care Specialists of Illinois - Decatur, Decatur
Decatur Memorial Hospital, Decatur
Illinois CancerCare-Dixon, Dixon
Carle Physician Group-Effingham, Effingham
Crossroads Cancer Center, Effingham
Illinois CancerCare-Eureka, Eureka
Illinois CancerCare-Galesburg, Galesburg
Northwestern Medicine Cancer Center Delnor, Geneva
Northwestern Medicine Glenview Outpatient Center, Glenview
Northwestern Medicine Grayslake Outpatient Center, Grayslake
Edward Hines Jr VA Hospital, Hines
Illinois CancerCare-Kewanee Clinic, Kewanee
Northwestern Medicine Lake Forest Hospital, Lake Forest
Illinois CancerCare-Macomb, Macomb
Carle Physician Group-Mattoon/Charleston, Mattoon
Loyola University Medical Center, Maywood
Cancer Care Center of O'Fallon, O'Fallon
Northwestern Medicine Oak Brook, Oak Brook
Northwestern Medicine Orland Park, Orland Park
Illinois CancerCare-Ottawa Clinic, Ottawa
Illinois CancerCare-Pekin, Pekin
Illinois CancerCare-Peoria, Peoria
Illinois CancerCare-Peru, Peru
Illinois CancerCare-Princeton, Princeton
Memorial Hospital East, Shiloh
Southern Illinois University School of Medicine, Springfield
Springfield Clinic, Springfield
Springfield Memorial Hospital, Springfield
Carle Cancer Center, Urbana
Northwestern Medicine Cancer Center Warrenville, Warrenville
Illinois CancerCare - Washington, Washington
IndianaIndiana University/Melvin and Bren Simon Cancer Center, Indianapolis
IowaMary Greeley Medical Center, Ames
McFarland Clinic - Ames, Ames
UI Health Care Mission Cancer and Blood - Ankeny Clinic, Ankeny
UI Health Care Mission Cancer and Blood - West Des Moines Clinic, Clive
Iowa Methodist Medical Center, Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic, Des Moines
McFarland Clinic - Trinity Cancer Center, Fort Dodge
McFarland Clinic - Marshalltown, Marshalltown
UI Health Care Mission Cancer and Blood - Waukee Clinic, Waukee
KansasUniversity of Kansas Clinical Research Center, Fairway
HaysMed, Hays
University of Kansas Cancer Center, Kansas City
Lawrence Memorial Hospital, Lawrence
The University of Kansas Cancer Center - Olathe, Olathe
University of Kansas Cancer Center-Overland Park, Overland Park
University of Kansas Hospital-Indian Creek Campus, Overland Park
Salina Regional Health Center, Salina
University of Kansas Health System Saint Francis Campus, Topeka
University of Kansas Hospital-Westwood Cancer Center, Westwood
KentuckyUniversity of Kentucky/Markey Cancer Center, Lexington
MaineLafayette Family Cancer Center-EMMC, Brewer
MarylandKaiser Permanente-Woodlawn Medical Center, Baltimore
Kaiser Permanente-Gaithersburg Medical Center, Gaithersburg
Kaiser Permanente - Largo Medical Center, Largo
Kaiser Permanente Lutherville - Timonium Medical Center, Lutherville
MassachusettsUMass Memorial Medical Center - University Campus, Worcester
MichiganTrinity Health Saint Joseph Mercy Hospital Ann Arbor, Ann Arbor
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton
Trinity Health Medical Center - Brighton, Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton, Canton
Trinity Health Medical Center - Canton, Canton
Chelsea Hospital, Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital, Chelsea
Cancer Hematology Centers - Flint, Flint
Genesys Hurley Cancer Institute, Flint
Hurley Medical Center, Flint
University of Michigan Health - Sparrow Lansing, Lansing
Trinity Health Saint Mary Mercy Livonia Hospital, Livonia
Trinity Health Saint Joseph Mercy Oakland Hospital, Pontiac
MyMichigan Medical Center Saginaw, Saginaw
MyMichigan Medical Center Tawas, Tawas City
Huron Gastroenterology PC, Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti
MinnesotaSanford Joe Lueken Cancer Center, Bemidji
Essentia Health - Deer River Clinic, Deer River
Essentia Health Cancer Center, Duluth
Essentia Health Hibbing Clinic, Hibbing
Essentia Health Sandstone, Sandstone
Essentia Health Virginia Clinic, Virginia
MississippiBaptist Memorial Hospital and Cancer Center-Golden Triangle, Columbus
Baptist Cancer Center-Grenada, Grenada
Baptist Memorial Hospital and Cancer Center-Union County, New Albany
Baptist Memorial Hospital and Cancer Center-Oxford, Oxford
Baptist Memorial Hospital and Cancer Center-Desoto, Southhaven
MissouriSaint Francis Medical Center, Cape Girardeau
Siteman Cancer Center at Saint Peters Hospital, City of Saint Peters
Siteman Cancer Center at West County Hospital, Creve Coeur
University Health Truman Medical Center, Kansas City
University of Kansas Cancer Center - Briarcliff, Kansas City
University of Kansas Cancer Center - North, Kansas City
University of Kansas Cancer Center - Lee's Summit, Lee's Summit
Mercy Hospital South, St Louis
Siteman Cancer Center at Christian Hospital, St Louis
Siteman Cancer Center-South County, St Louis
Washington University School of Medicine, St Louis
MontanaCommunity Hospital of Anaconda, Anaconda
Billings Clinic Cancer Center, Billings
Bozeman Health Deaconess Hospital, Bozeman
Benefis Sletten Cancer Institute, Great Falls
Logan Health Medical Center, Kalispell
Community Medical Center, Missoula
NevadaOptumCare Cancer Care at Charleston, Las Vegas
OptumCare Cancer Care at Fort Apache, Las Vegas
New HampshireNew Hampshire Oncology Hematology PA-Concord, Concord
Solinsky Center for Cancer Care, Manchester
New JerseyMemorial Sloan Kettering Basking Ridge, Basking Ridge
Memorial Sloan Kettering Monmouth, Middletown
Memorial Sloan Kettering Bergen, Montvale
Virtua Samson Cancer Center, Moorestown
Virtua Voorhees, Voorhees Township
New YorkMemorial Sloan Kettering Commack, Commack
Memorial Sloan Kettering Westchester, Harrison
Memorial Sloan Kettering Cancer Center, New York
University of Rochester, Rochester
Memorial Sloan Kettering Nassau, Uniondale
North CarolinaFirstHealth of the Carolinas-Moore Regional Hospital, Pinehurst
North DakotaSanford Bismarck Medical Center, Bismarck
Sanford Broadway Medical Center, Fargo
Sanford Roger Maris Cancer Center, Fargo
OhioAultman Health Foundation, Canton
Miami Valley Hospital South, Centerville
Ohio State University Comprehensive Cancer Center, Columbus
Miami Valley Hospital, Dayton
Miami Valley Hospital North, Dayton
Premier Blood and Cancer Center, Dayton
Atrium Medical Center-Middletown Regional Hospital, Franklin
Miami Valley Cancer Care and Infusion, Greenville
ProMedica Flower Hospital, Sylvania
Upper Valley Medical Center, Troy
OklahomaCancer Centers of Southwest Oklahoma Research, Lawton
University of Oklahoma Health Sciences Center, Oklahoma City
OregonProvidence Newberg Medical Center, Newberg
Saint Alphonsus Cancer Care Center-Ontario, Ontario
Providence Willamette Falls Medical Center, Oregon City
Kaiser Permanente Northwest, Portland
Oregon Health and Science University, Portland
Providence Portland Medical Center, Portland
Providence Saint Vincent Medical Center, Portland
PennsylvaniaWellSpan Medical Oncology and Hematology, Chambersburg
Geisinger Medical Center, Danville
Geisinger Cancer Center Dickson City, Dickson City
Ephrata Cancer Center, Ephrata
Adams Cancer Center, Gettysburg
Sechler Family Cancer Center, Lebanon
Geisinger Medical Oncology-Lewisburg, Lewisburg
Community Medical Center, Scranton
Geisinger Wyoming Valley/Henry Cancer Center, Wilkes-Barre
Cancer Care Associates of York, York
WellSpan Health-York Cancer Center, York
WellSpan Health-York Hospital, York
South CarolinaAnMed Health Cancer Center, Anderson
South DakotaSanford Cancer Center Oncology Clinic, Sioux Falls
Sanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeBaptist Memorial Hospital and Cancer Center-Collierville, Collierville
Baptist Memorial Hospital and Cancer Center-Memphis, Memphis
TexasThe Don and Sybil Harrington Cancer Center, Amarillo
UtahHuntsman Cancer Institute/University of Utah, Salt Lake City
VirginiaKaiser Permanente Tysons Corner Medical Center, McLean
Kaiser Permanente-Caton Hill Medical Center, Woodbridge
WashingtonSwedish Cancer Institute-Edmonds, Edmonds
Swedish Cancer Institute-Issaquah, Issaquah
Swedish Medical Center-First Hill, Seattle
West VirginiaEdwards Comprehensive Cancer Center, Huntington
West Virginia University Healthcare, Morgantown
WisconsinDuluth Clinic Ashland, Ashland
Marshfield Medical Center-EC Cancer Center, Eau Claire
Gundersen Lutheran Medical Center, La Crosse
Marshfield Medical Center-Marshfield, Marshfield
Marshfield Medical Center - Minocqua, Minocqua
Marshfield Medical Center-Rice Lake, Rice Lake
Marshfield Medical Center-River Region at Stevens Point, Stevens Point
Marshfield Medical Center - Weston, Weston

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.