Targeted treatment for advanced lung cancer with a specific gene change
Official title: 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)
Run by SWOG Cancer Research Network · NCT06031688 · Data updated 2026-11-12
This study is testing if a new lung cancer treatment called tepotinib, with or without another drug called ramucirumab, can help people with advanced non-small cell lung cancer that has a specific gene change.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Minutes and up |
| Sex | All |
| Enrollment | 56 (estimated) |
| Sponsor | SWOG Cancer Research Network Research network |
| Drugs / interventions | bevacizumab, ramucirumab, crizotinib, tivantinib, savolitinib, tepotinib, cabozantinib, foretinib, chemotherapy, immunotherapy, radiation |
| Locations | 278 sites (Daphne, Alabama and 277 other locations) |
| Status | Recruiting |
| Started | August 8, 2024 |
| Main results expected | May 31, 2028 |
| Study ends | May 31, 2028 |
| Registry record updated | October 9, 2026 |
| Trial ID | NCT06031688 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are patients with stage IV or recurrent non-small cell lung cancer that have a documented MET exon 14 skipping mutation.
✕Probably not a fit
Patients without the MET exon 14 skipping mutation or those with other types of lung cancer may not benefit from this treatment.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase II trial evaluates the effectiveness of tepotinib, with or without ramucirumab, in treating patients with advanced non-small cell lung cancer (NSCLC) that has a MET exon 14 skipping mutation. Participants will be randomized into two groups: one receiving both tepotinib and ramucirumab, and the other receiving only tepotinib. The study aims to compare response rates, progression-free survival, and overall survival between the two treatment arms. Additionally, it will assess treatment-related side effects and establish a tissue/blood repository for future research.
Why it matters
Potential benefit: If successful, this treatment could significantly improve outcomes for patients with advanced lung cancer harboring the MET exon 14 skipping mutation.
How similar studies have gone: Other studies have shown promising results with targeted therapies for specific mutations in lung cancer, indicating potential success for this approach.
Who can join: the full rules
Show full inclusion / exclusion 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
Where it's running
-
Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
Daphne, Alabama, United States Recruiting -
Thomas Hospital
Fairhope, Alabama, United States Recruiting -
Mobile Infirmary Medical Center
Mobile, Alabama, United States Recruiting -
Gulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
Saraland, Alabama, United States Recruiting -
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States Recruiting -
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States Recruiting
Show 44 more locations
-
Sutter Auburn Faith Hospital
Auburn, California, United States Recruiting -
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States Recruiting -
Tower Cancer Research Foundation
Beverly Hills, California, United States Recruiting -
Palo Alto Medical Foundation-Fremont
Fremont, California, United States Recruiting -
UC San Diego Moores Cancer Center
La Jolla, California, United States Recruiting -
Cedars-Sinai Medical Center
Los Angeles, California, United States Recruiting -
Memorial Medical Center
Modesto, California, United States Recruiting -
Palo Alto Medical Foundation Health Care
Palo Alto, California, United States Recruiting -
Eisenhower Medical Center
Rancho Mirage, California, United States Recruiting -
Sutter Roseville Medical Center
Roseville, California, United States Recruiting -
Sutter Medical Center Sacramento
Sacramento, California, United States Recruiting -
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States Recruiting -
California Pacific Medical Center-Pacific Campus
San Francisco, California, United States Recruiting -
Kaiser Permanente-San Francisco
San Francisco, California, United States Recruiting -
Mills Health Center
San Mateo, California, United States Recruiting -
Palo Alto Medical Foundation-Santa Cruz
Santa Cruz, California, United States Recruiting -
Sutter Pacific Medical Foundation
Santa Rosa, California, United States Recruiting -
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, United States Recruiting -
Cedars-Sinai Cancer - Tarzana
Tarzana, California, United States Recruiting -
Torrance Memorial Physician Network - Cancer Care
Torrance, California, United States Recruiting -
Kaiser Permanente-Vallejo
Vallejo, California, United States Recruiting -
Sutter Solano Medical Center/Cancer Center
Vallejo, California, United States Recruiting -
UCHealth University of Colorado Hospital
Aurora, Colorado, United States Recruiting -
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, United States Recruiting -
Memorial Hospital North
Colorado Springs, Colorado, United States Recruiting -
Poudre Valley Hospital
Fort Collins, Colorado, United States Recruiting -
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, United States Recruiting -
UCHealth Greeley Hospital
Greeley, Colorado, United States Recruiting -
Medical Center of the Rockies
Loveland, Colorado, United States Recruiting -
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, United States Recruiting -
Yale University
New Haven, Connecticut, United States Recruiting -
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, United States Recruiting -
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, United States Recruiting -
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, United States Recruiting -
Bayhealth Hospital Kent Campus
Dover, Delaware, United States Recruiting -
Bayhealth Hospital Sussex Campus
Milford, Delaware, United States Recruiting
+228 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Principal investigator: Paul K Paik — SWOG Cancer Research Network
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
Combining cemiplimab with standard treatment for advanced lung cancer
This study is testing if adding the immunotherapy drug cemiplimab to standard treatments can help people with advanced lung cancer live longer and feel better compared to just the standard treatments alone.
-
Comparing targeted drug combinations for advanced lung cancer with specific gene changes
This study is testing different combinations of targeted drugs to see if they can help people with advanced lung cancer that has specific gene changes live longer and feel better.
-
Advanced NSCLC with actionable mutations after targeted therapy and chemo: expanded Lung-MAP treatment
This phase II trial tests whether sacituzumab govitecan alone, ivonescimab alone, or the combination of both can help people with advanced or recurrent NSCLC that has a targetable genetic change.
-
SX-682 with Atezolizumab for advanced or metastatic NSCLC
This phase 2 trial tests whether combining SX-682 with atezolizumab can help people with advanced, metastatic, or recurrent NSCLC who have progressed after prior treatments.
-
Combining SX-682 and Pembrolizumab for Advanced Lung Cancer Treatment
This study is testing if a new oral medication called SX-682, when combined with the IV drug pembrolizumab, can help people with advanced lung cancer feel better and improve their treatment outcomes.
-
Combining PBF-1129 and Nivolumab for Advanced Lung Cancer Treatment
This study is testing a new combination of two drugs, PBF-1129 and nivolumab, to see if it can help people with advanced lung cancer live longer and feel better.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.