Comparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)

Inclusion Criteria:

• Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMONELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven MasterProtocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)

• Participants must have been assigned to S1900G by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900G isdetermined by the LUNGMAP protocol

• Participants must have documentation of NSCLC with a sensitizing EGFR mutation andhave radiologically or clinically progressed (in the opinion of the treatingphysician) on osimertinib, alone or in combination with other agent(s), as theirmost recent line of therapy. Any number of prior lines of therapy is allowed

• Participants must have a MET amplification determined by tissue-based or blood-based (circulating tumor DNA [ctDNA]) next generation sequencing (NGS) assay. METamplifications may have been determined based on tissue submitted for testing byFoundation Medicine Inc (FMI) through the LUNGMAP screening protocol or using testresults completed outside of the study. Tissue or blood must be obtained afterdisease progression on osimertinib (alone or in combination with another agent[s]).The testing must be done within a laboratory with Clinical Laboratory ImprovementAct (CLIA), International Organization for Standardization (ISO)/Independent EthicsCommittee (IEC), College of American Pathologists (CAP), or similar certification

• Note: Participants previously tested for and determined to have MET amplifiedNSCLC, at the time of progression on osimertinib, outside of LUNGMAP, must alsosubmit tissue for central FMI testing on the LUNGMAP screening protocol, ifavailable

• Participants must have either measurable disease or non-measurable diseasedocumented by CT or MRI. The CT from a combined PET/CT may be used to document onlynon-measurable disease unless it is of diagnostic quality. Measurable disease mustbe assessed within 28 days prior to sub-study randomization. Non-measurable diseasemust be assessed within 42 days prior to sub-study randomization. All known sites ofdisease must be assessed and documented on the Baseline Tumor Assessment Form.Participants whose only measurable disease is within a previous radiation therapyport must demonstrate clearly progressive disease (in the opinion of the treatinginvestigator) prior to sub-study randomization to be considered measurable

• Participants must have a CT with contrast or MRI scan of the brain to evaluate forcentral nervous system (CNS) disease within 42 days prior to sub-study randomization

• Participants with symptomatic CNS metastasis (brain metastases or leptomeningealdisease) must be neurologically stable and have a stable or decreasingcorticosteroid requirement for at least 5 days before sub-study randomization

• Participants must have recovered (=< grade 1) from any side effects of priortherapy, except for alopecia and vitiligo

• Participants must be able to swallow tablets whole

• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to sub-studyrandomization)

• 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 ofGilbert's disease (within 28 days prior to sub-study randomization). Participantswith history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 xinstitutional ULN. Participants with history of liver metastasis must have AST =< 5x ULN (within 28 days prior to sub-study randomization)

• Participants must have a serum creatinine =< the IULN OR calculated creatinineclearance >= 50 mL/min using the following Cockcroft-Gault Formula. This specimenmust have been drawn and processed within 28 days prior to sub-study randomization

• Participants' most recent Zubrod performance status must be 0-1 and be documentedwithin 28 days prior to sub-study randomization

• Participants must have an electrocardiogram (ECG) performed, with a Fridericia'sCorrection Formula (QTcF) =< 470 msec, within 28 days prior to sub-studyrandomization. It is suggested that a local cardiologist review the QTcF intervals

• Participants must have a completed medical history and physical exam within 28 daysprior to sub-study randomization

• Participants must have a urinalysis performed 28 days prior to sub-studyrandomization. Participant must have a urinary protein =< 1+ on dipstick or routineurinalysis (UA). Random analysis of urine protein with a normal value is sufficient.If urine dipstick or routine analysis indicated proteinuria >= 2+, then a 24-hoururine is to be collected and demonstrate < 2000 mg of protein in 24 hours to allowparticipation in the study

• Participants must have an International Normalized Ratio (INR) =< 1.5 seconds abovethe institutional upper limit of normal (IULN) (unless receiving anticoagulationtherapy) documented within 28 days to sub-study randomization. Participants musthave a partial thromboplastin time (PTT) =< 5 seconds above the 'institutional upperlimit of normal (IULN) (unless receiving anticoagulation therapy) documented within 28 days prior to sub-study randomization

• Participants with known human immunodeficiency virus (HIV) infection must be oneffective anti-retroviral therapy at randomization and have undetectable viral loadwithin 6 months prior to sub-study randomization

• Participants must have asymptomatic serum amylase =< 2 x ULN and serum lipase =< ULNobtained within 28 days prior to sub-study randomization. Asymptomatic is defined ashaving no signs and/ or symptoms suggesting pancreatitis or pancreatic injury (e.g.elevated P. amylase, abnormal imaging findings of pancreas, etc.)

• Participants must have adequate cardiac function. Participants with known history orcurrent symptoms of cardiac disease, or history of treatment with cardiotoxicagents, must have a clinical risk assessment of cardiac function using the New YorkHeart Association Functional Classification. To be eligible for this trial,participants must be class 2B or better

• Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)

• Participants must also be offered participation in specimen banking. Withparticipant consent, specimens must be collected and submitted via the SWOG SpecimenTracking System

• Note: As a part of the OPEN registration process the treating institution's identityis provided in order to ensure that the current (within 365 days) date ofinstitutional review board approval for this study has been entered in the system

• Participants must be informed of the investigational nature of this study and mustsign and give informed consent in accordance with institutional and federalguidelines

• Participants with impaired decision-making capacity must not have a neurological orpsychological condition that precludes their safe participation in the study (e.g.,tracking pill consumption and reporting adverse events to the investigator). Forparticipants with impaired decision-making capabilities, legally authorizedrepresentatives may sign and give informed consent on behalf of study participantsin accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Exclusion Criteria:

• Participants must not have received an anti-VEGF or VEGFR inhibitor or MET inhibitor

• Participants must not have received any anti-cancer drug (investigational orstandard of care drug, except osimertinib) within 21 days prior to sub-studyrandomization

• Note: osimertinib may continue up to the day prior to study treatmentinitiation

• Participants must not have received any radiation therapy within 14 days prior tosub-study randomization

• Participants must not be planning to receive any concurrent chemotherapy,immunotherapy, biologic or hormonal therapy for cancer treatment while receivingtreatment on this study

• Participants must not have had a major surgery within 14 days prior to sub-studyrandomization. Participants must have fully recovered from the effects of priorsurgery in the opinion of the treating investigator

• Participants must not have received a live attenuated vaccination within 28 daysprior to sub-study randomization. All COVID-19 vaccines that have received Food andDrug Administration (FDA) approval or FDA emergency use authorization are acceptable

• Participants must not have received strong inducers of CYP3A4 (including herbalsupplements such as St. John's Wort); CYP3A4 inhibitors; CYP1A2 substrates; P-gp andBCRP substrates; sensitive substrates of MATE1 and MATE2K; or drugs that are knownto prolong QT interval within 7 days prior to sub-study registration and must not beplanning to use any of these throughout protocol treatment

• Participants must not have uncontrolled blood pressure and hypertension within 28days prior to sub-study randomization

• Participants must not have a prior or concurrent malignancy whose natural history ortreatment (in the opinion of the treating physician) has the potential to interferewith the safety or efficacy assessment of the investigational regimen

• Participants must not be pregnant or breastfeeding (nursing includes breast milk fedto an infant by any means, including from the breast, milk expressed by hand, orpumped). Individuals who are of reproductive potential must have agreed to use aneffective contraceptive method with details provided as a part of the consentprocess. A person who has had menses at any time in the preceding 12 consecutivemonths or who has semen likely to contain sperm is considered to be of "reproductivepotential." In addition to routine contraceptive methods, "effective contraception"also includes refraining from sexual activity that might result in pregnancy andsurgery intended to prevent pregnancy (or with a side-effect of pregnancyprevention) including hysterectomy, bilateral oophorectomy, bilateral tuballigation/occlusion, and vasectomy with testing showing no sperm in the semen