Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)
Purpose
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.
Conditions
- Recurrent Lung Non-Small Cell Carcinoma
- Stage IV Lung Cancer AJCC v8
Eligibility
- Eligible Ages
- All ages
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 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 NOTE: Participants previously tested for and determined to have a MET
exon 14 skipping mutation, outside of LUNGMAP, must also submit tissue for
central Foundation Medicine (FMI) testing on the LUNGMAP screening protocol, if
available
- 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 must have progressed (in the opinion of the treating physician)
following the most recent line of therapy
- Participants must have received at least one line of systemic treatment for Stage IV
or recurrent NSCLC
- Participants must have recovered (=< grade 1) from any side effects of prior therapy
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
- Participants must be able to swallow tablets whole
- 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 =< 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
- 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 have a Lymphoscintigraphy scan performed within 28 days prior to
sub-study randomization
- 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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm A: (Ramucirumab and tepotinib) |
Patients receive ramucirumab IV over 30-60 minutes on day 1 of each cycle and 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 undergo lymphoscintigraphy scan and CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study. |
|
|
Active Comparator Arm B: (Tepotinib) |
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 undergo lymphoscintigraphy scan and CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study. |
|
Recruiting Locations
Jonesboro, Arkansas 72401
Little Rock, Arkansas 72205
Site Public Contact
501-686-8274
Anaheim, California 92806
Auburn, California 95602
Baldwin Park, California 91706
Bellflower, California 90706
Berkeley, California 94704
Beverly Hills, California 90211
Fontana, California 92335
Fremont, California 94538
Harbor City, California 90710
Irvine, California 92618
Los Angeles, California 90027
Los Angeles, California 90034
Los Angeles, California 90048
Site Public Contact
310-423-8965
Modesto, California 95355
Ontario, California 91761
Palo Alto, California 94301
Panorama City, California 91402
Riverside, California 92505
Roseville, California 95661
Sacramento, California 95816
Sacramento, California 95817
Site Public Contact
916-734-3089
San Diego, California 92120
San Francisco, California 94115
San Marcos, California 92078
Santa Cruz, California 95065
Santa Rosa, California 95403
Sunnyvale, California 94086
Tarzana, California 91356
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818-981-3818
Torrance, California 90505
Vallejo, California 94589
Woodland Hills, California 91367
Aurora, Colorado 80045
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720-848-0650
Colorado Springs, Colorado 80909
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719-365-2406
Colorado Springs, Colorado 80920
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719-364-6700
Fort Collins, Colorado 80524
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970-297-6150
Fort Collins, Colorado 80528
Loveland, Colorado 80538
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970-203-7083
Derby, Connecticut 06418
Fairfield, Connecticut 06824
Glastonbury, Connecticut 06033
Greenwich, Connecticut 06830
Guilford, Connecticut 06437
Hartford, Connecticut 06105
New Haven, Connecticut 06520
North Haven, Connecticut 06473
Stamford, Connecticut 06902
Torrington, Connecticut 06790
Trumbull, Connecticut 06611
Waterbury, Connecticut 06708
Waterford, Connecticut 06385
Washington, District of Columbia 20002
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301-548-5743
Gainesville, Georgia 30501
Boise, Idaho 83706
Caldwell, Idaho 83605
Coeur d'Alene, Idaho 83814
Nampa, Idaho 83687
Post Falls, Idaho 83854
Sandpoint, Idaho 83864
Bloomington, Illinois 61704
Canton, Illinois 61520
Carthage, Illinois 62321
Chicago, Illinois 60611
Danville, Illinois 61832
Decatur, Illinois 62526
Decatur, Illinois 62526
Dixon, Illinois 61021
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815-285-7800
Effingham, Illinois 62401
Effingham, Illinois 62401
Eureka, Illinois 61530
Galesburg, Illinois 61401
Hines, Illinois 60141
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708-202-8387
Kewanee, Illinois 61443
Macomb, Illinois 61455
Mattoon, Illinois 61938
O'Fallon, Illinois 62269
Ottawa, Illinois 61350
Pekin, Illinois 61554
Peoria, Illinois 61615
Peru, Illinois 61354
Princeton, Illinois 61356
Shiloh, Illinois 62269
Springfield, Illinois 62702
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217-545-7929
Springfield, Illinois 62702
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Urbana, Illinois 61801
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Indianapolis, Indiana 46202
Ames, Iowa 50010
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515-956-4132
Ames, Iowa 50010
Ankeny, Iowa 50023
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Boone, Iowa 50036
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Des Moines, Iowa 50309
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Des Moines, Iowa 50309
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Fort Dodge, Iowa 50501
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Jefferson, Iowa 50129
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Marshalltown, Iowa 50158
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515-956-4132
Fairway, Kansas 66205
Hays, Kansas 67601
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785-623-5774
Kansas City, Kansas 66160
Lawrence, Kansas 66044
Olathe, Kansas 66061
Overland Park, Kansas 66210
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Topeka, Kansas 66606
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785-295-8000
Westwood, Kansas 66205
Lexington, Kentucky 40536
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Baltimore, Maryland 21244
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301-816-7218
Gaithersburg, Maryland 20879
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301-816-7218
Largo, Maryland 20774
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301-816-7446
Lutherville, Maryland 21093
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410-847-3000
Ann Arbor, Michigan 48106
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Canton, Michigan 48188
Canton, Michigan 48188
Chelsea, Michigan 48118
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Flint, Michigan 48503
Flint, Michigan 48503
Flint, Michigan 48503
Flint, Michigan 48503
Livonia, Michigan 48154
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Bemidji, Minnesota 56601
Deer River, Minnesota 56636
Duluth, Minnesota 55805
Hibbing, Minnesota 55746
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218-786-3308
Sandstone, Minnesota 55072
Virginia, Minnesota 55792
Columbus, Mississippi 39705
Grenada, Mississippi 38901
New Albany, Mississippi 38652
Oxford, Mississippi 38655
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Cape Girardeau, Missouri 63703
Creve Coeur, Missouri 63141
Kansas City, Missouri 64108
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816-404-4375
Kansas City, Missouri 64111
Kansas City, Missouri 64154
Lee's Summit, Missouri 64064
Lee's Summit, Missouri 64086
North Kansas City, Missouri 64116
Saint Louis, Missouri 63110
Saint Louis, Missouri 63129
Saint Louis, Missouri 63136
Saint Peters, Missouri 63376
Anaconda, Montana 59711
Billings, Montana 59101
Bozeman, Montana 59715
Great Falls, Montana 59405
Kalispell, Montana 59901
Missoula, Montana 59804
Henderson, Nevada 89052
Las Vegas, Nevada 89102
Las Vegas, Nevada 89148
Concord, New Hampshire 03301
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603-224-2556
Manchester, New Hampshire 03103
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Basking Ridge, New Jersey 07920
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Moorestown, New Jersey 08057
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Commack, New York 11725
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Cooperstown, New York 13326
Harrison, New York 10604
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New York, New York 10065
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Rochester, New York 14642
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Uniondale, New York 11553
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Bismarck, North Dakota 58501
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Canton, Ohio 44710
Centerville, Ohio 45459
Dayton, Ohio 45409
Dayton, Ohio 45409
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937-276-8320
Dayton, Ohio 45415
Franklin, Ohio 45005-1066
Greenville, Ohio 45331
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937-569-7515
Sylvania, Ohio 43560
Troy, Ohio 45373
Lawton, Oklahoma 73505
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877-231-4440
Oklahoma City, Oklahoma 73104
Newberg, Oregon 97132
Ontario, Oregon 97914
Oregon City, Oregon 97045
Portland, Oregon 97213
Portland, Oregon 97225
Portland, Oregon 97239
Chambersburg, Pennsylvania 17201
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717-217-6020
Danville, Pennsylvania 17822
Ephrata, Pennsylvania 17522
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717-721-4840
Gettysburg, Pennsylvania 17325
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877-441-7957
Lebanon, Pennsylvania 17042
Lewisburg, Pennsylvania 17837
Scranton, Pennsylvania 18510
Wilkes-Barre, Pennsylvania 18711
York, Pennsylvania 17403
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717-741-9229
York, Pennsylvania 17403
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877-441-7957
York, Pennsylvania 17403
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Sioux Falls, South Dakota 57104
Sioux Falls, South Dakota 57117-5134
Collierville, Tennessee 38017
Memphis, Tennessee 38120
Amarillo, Texas 79106
McLean, Virginia 22102
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240-632-4284
Woodbridge, Virginia 22192
Edmonds, Washington 98026
Issaquah, Washington 98029
Seattle, Washington 98122
Huntington, West Virginia 25701
Ashland, Wisconsin 54806
Eau Claire, Wisconsin 54701
La Crosse, Wisconsin 54601
Marshfield, Wisconsin 54449
Minocqua, Wisconsin 54548
Stevens Point, Wisconsin 54482
Weston, Wisconsin 54476
More Details
- NCT ID
- NCT06031688
- Status
- Recruiting
- Sponsor
- SWOG Cancer Research Network
Detailed Description
PRIMARY OBJECTIVE: I. To compare the response rate (confirmed or unconfirmed, complete or impartial) 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 undergo lymphoscintigraphy scan and computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection while 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.