UAMS - Translational Research Institute

Condition

• Lung Non-Small Cell Carcinoma

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

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 is unstable in the
opinion of the treating investigator

- 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

Detailed Description

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-SC 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 subcutaneously (SC) on days 1, 8, 15, and 22 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.