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 Sex
- 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 4116834, Arkansas 4099753 72401
Little Rock 4119403, Arkansas 4099753 72205
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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.