This study will evaluate the efficacy of crizotinib as induction therapy in participants with surgically resectable ALK rearrangement, ROS1 rearrangement, or MET exon 14 mutation positive NSCLC.

Participants with stage IA-IIIA, surgically resectable lung adenocarcinoma with an activating alteration in ALK, ROS1 or MET will receive neoadjuvant treatment with crizotinib. This neoadjuvant treatment will last 6 weeks and on the last day of dosing of crizotinib, participants will undergo surgical resection, followed by 5 years of follow-up via chart review.

Inclusion Criteria:

1. Stage IA-IIIA NSCLC by 8th edition AJCC staging (that is deemed to be surgically resectable by a board certified thoracic surgeon.

2. Staging by PET-CT scan and MRI brain showing no evidence of metastatic disease (mediastinoscopy is not required unless imaging is indeterminate and is then considered standard of care)

3. Documented evidence of an ALK rearrangement (by FISH, IHC, or NGS), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a CLIA-approved laboratory.

4. Measurable disease defined by RECIST 1.1 criteria.

5. Life expectancy of at least 24 months.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

7. Age ≥ 18 years

8. Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females

9. Adequate organ function:

   • Absolute neutrophil count (ANC) ≥1500/µL
   • Platelets ≥75,000/µL
   • Hemoglobin ≥ 10g/dL
   • AST /ALT ≤ 2.5 x upper limit of normal (ULN)
   • Total serum bilirubin ≤ 1.5 x ULN
   • Serum creatinine ≤ 1.5 x UNL
   • Serum amylase/lipase ≤ 1.5 x UNL

10. Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing potential.

11. If fertile, willing to use highly effective form of contraception (defined as a combination of at least two of the following methods: condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during the dosing period and for at least 4 months after the dosing period.

12. Ability to provide signed informed consent and willing and able to comply with all study requirements.

Exclusion Criteria:

1. Stage IIIB or IV NSCLC.

2. History or the presence of pulmonary interstitial disease, or drug-related pneumonitis.

3. Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug

4. Inability to swallow oral medications

5. Have significant, uncontrolled or active cardiovascular disease, specifically including but restricted to:

   • Myocardial infarction (MI) within 6 months of trial enrollment
   • Unstable angina within 6 months of trial enrollment
   • Congestive heart failure (CHF) with 6 months prior to trial enrollment
   • Any history of ventricular arrhythmia
   • Cerebrovascular accident or transient ischemic attack within 6 months of D1 of treatment
   • Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate < 50 beat per minute
   • Uncontrolled hypertension defined as baseline SBP> 160 and DBP > 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathy

6. Have active infection requiring antibiotics

7. Pregnant or lactating female.

8. Prior treatment with an ALK, ROS1 or MET inhibitor

9. Any prior anticancer therapy for this diagnosis

10. Any active cancer diagnosis (basal or squamous cell cancers allowed) within the last 5 years for which the patient is receiving active therapy or which is untreated. Any cancer diagnosis within the last 5 years that is considered "treated" and/ or on surveillance may be included in the trial.

11. Have any condition or illness that, in the opinion of the investigator would compromise patient safety or interfere with evaluation of the study drug (including but not limited to HIV and HCV)

Participants eligible for this study will be newly diagnosed with stage IA-IIIA NSCLC and who harbor an activating alteration in ALK, ROS1, or the MET gene

3 years