Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial)

Study Overview
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Brief Summary
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This phase II Expanded Lung-MAP treatment trial tests how well amivantamab-vmjw works in treating patients patients with MET amplification non-small cell lung cancer. Amivantamab-vmjw is a drug that reduces extra copies of the MET gene, a change present in your tumor. Giving amivantamab-vmjw may lower the chance of the growth or spread of advanced non-small cell lung cancer that has extra copies of the MET gene in the tumor.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial) in participants with MET amplification-positive non-small cell lung cancer (NSCLC) treated with amivantamab (amivantamab-vmjw) within each cohort. SECONDARY OBJECTIVES: I. To evaluate progression-free survival (PFS) within each cohort. II. To evaluate overall survival (OS) within each cohort. III. To evaluate the duration of response among responders within each cohort. IV. To evaluate the frequency and severity of toxicities within each cohort and combined across all study participants. TRANSLATIONAL MEDICINE OBJECTIVES: I. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) prior to treatment on Cycle 1 Day 1, Cycle 3 Day 1, and at first progression for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor deoxyribonucleic acid (ctDNA). II. To establish a tissue/blood repository from participants with refractory non-small cell lung cancer (NSCLC). OUTLINE: Patients receive amivantamab intravenously (IV) on days 1 and 2 in week and once a week in weeks 2-4 of cycle 1 and then on days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computerized tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up for up to 3 years.

Official Title
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A Phase II Study of Amivantamab in Participants With MET Amplification-Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP SUB-STUDY)

Conditions
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Lung Non-Small Cell Carcinoma

Intervention / Treatment
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* Biological: Amivantamab
* Procedure: Biospecimen Collection
* Procedure: Computed Tomography
* Procedure: Magnetic Resonance Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have been assigned to S1900J by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900J is determined by the LUNGMAP protocol Participants must have documentation of NSCLC with MET amplification determined by FMI tissue-based next generation sequencing (NGS) assay 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 registration. 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 registration. 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 registration 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 registration Participants with asymptomatic CNS metastasis (brain metastases or leptomeningeal disease) must be clinically stable and asymptomatic for at least 14 days prior to sub-study registration NOTE: Participants can be on a low-dose corticosteroid treatment (≤ 10 mg prednisone or equivalent) for at least 14 days prior to study treatment Participants must not have other known actionable oncogenic alterations, such as (but not limited to) EGFR sensitizing mutations, EGFR T790M mutation, MET Exon-14 skipping mutant NSCLC, 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. The exception is if a side effect from a prior treatment is known to be permanent without expected further recovery or resolution (i.e., endocrinopathy from immunotherapy or cisplatin neurotoxicity) Participants must not have been previously treated for any cancer with MET tyrosine kinase inhibitors (TKIs) such as tepotinib, capmatinib, and crizotinib Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration Participants must not have a prior treatment with anti-PD-1 or anti-PD-L1 antibody within 6 weeks of sub-study registration Participants must not have received any radiation therapy within 14 days prior to sub-study registration 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 major surgery excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 28 days prior to sub-study registration, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate 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 registration) Hemoglobin >= 10.0 g/dL (within 28 days prior to sub-study registration) Platelets ≥ 75 x 10^3/uL (within 28 days prior to sub-study registration) 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 registration) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × institutional ULN. Participants with history of liver metastasis must have AST and ALT ≤ 5 x ULN (within 28 days prior to sub-study registration) Participants must have a serum creatinine ≤ the institutional upper limit of normal (IULN) or calculated creatinine clearance ≥ 45 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to sub-study registration. For creatinine clearance formula see the tools on the CRA Workbench Participants' most recent Zubrod performance status must be 0-2 and be documented within 28 days prior to sub-study registration Participants must have a completed medical history and physical exam within 28 days prior to sub-study registration 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 registration 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 registration 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 registration Participants with known diabetes as determined by the treating investigator must show evidence of controlled disease within 14 days prior to sub-study registration Participants of reproductive potential must have a negative serum pregnancy test within 7 days prior to sub-study registration Participants must not have other clinically active infectious liver disease Participants must not have clinically significant hypertension within 28 days prior to sub-study registration as determined by the treating investigator Participants must not have a history of pneumonitis that required drug therapy or an active symptomatic interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis Participants must not have ongoing or active infection or be diagnosed or suspected viral infection as determined by the treating investigator. NOTE: Participants that have an infection requiring antimicrobial therapy will be required to complete antibiotics 1 week prior to starting treatment Participants must not have active bleeding diathesis as determined by the treating investigator Participants must not have impaired oxygenation requiring continuous oxygen supplementation as determined by the treating investigator Participants must not have psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements as determined by the treating investigator Participants must not have any ophthalmologic condition that in the opinion of the treating investigator could worsen with treatment with amivantamab-vmjw not limited to dry eyes, blurred vision, eye pruritus, visual impairment, aberrant eyelash growth, ocular hyperemia, conjunctival hyperemia, blepharitis, and uveitis 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 agree to have blood specimens submitted for circulating tumor DNA (ctDNA) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (amivantamab)<br>Patients receive amivantamab IV on days 1 and 2 in week and once a week in weeks 2-4 of cycle 1 and then on days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial. | Biological: Amivantamab<br>* Given IV<br>* Other names: Rybrevant;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Computed Tomography<br>* Undergo CT scan<br>* Other names: tomography;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate for amivantamab-vmjw | Response rates and associated confidence intervals will be calculated. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times. | Up to 3 years | 
| Progression free survival | Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times. | Up to 3 years | 
| Duration of response | Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times. | Up to 3 years | 
| Incidence of adverse events | Toxicity will be evaluated among all participants enrolled on the study (combining the squamous and non-squamous cohorts). With 80 participants, any toxicity can be estimated to within 11% with 95% confidence. Any toxicity with at least 5% prevalence has at least a 98% chance of being observed. | Up to 28 days |