Inclusion Criteria:

          1. Histologically or cytologically confirmed recurrent, metastatic NSCLC.

          2. Documented EGFR exon 20 insertion mutation may be demonstrated by:

               1. An FDA-approved device including cobas EGFR Mutation Test v2, therascreen EGFR
                  RGQ PCR Kit, FoundationOne CDx, or MSK-IMPACT, or

               2. A device or test validated and accepted by regulatory health authorities outside
                  the United States for patients enrolled in the trial outside of the United
                  States.

          3. At least one prior treatment with platinum-based chemotherapy. Note: Prior treatment
             with a PD-1/PD-L1 inhibitor is allowed but not required.

          4. Measurable disease by RECIST 1.1.

          5. Age ≥ 18 years.

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

          7. Ability to take pills by mouth.

          8. Have the following laboratory values:

               1. Serum creatinine < 1.5 × ULN or if higher than normal range, calculated
                  creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (by Cockroft-Gault
                  formula); actual body weight must be used for CrCl unless BMI > 30 kg/m2 then
                  lean body weight must be used.

               2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.

               3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due
                  to liver involvement by tumor.

               4. Hemoglobin ≥ 9.0 g/dL.

               5. Platelets ≥ 100 × 109 cells/L.

               6. Absolute neutrophil count ≥ 1.5 ×109 cells/L.

          9. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Accelerated Titration Patients Only

             a. Any EGFR tyrosine kinase inhibitors (TKIs), e.g., gefitinib, erlotinib, afatinib,
             and osmertinib, ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is
             longer, prior to the first dose of study drug on C1D1.

          2. Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only

             Prior treatment with any of the following:

               1. An EGFR-TKI of > 6 months in which the patient derived clinical benefit.

               2. An EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788) for > 2
                  cycles or discontinuation due to progressive disease.

             Note: Patients that discontinued an EGFR 20 insertion-targeting inhibitor for other
             reasons (e.g, intolerability) and have received ≤ 2 cycles of treatment may not be
             excluded upon agreement between the Investigator and Sponsor.

          3. All Patients

             Treatment with any of the following:

               1. Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days
                  prior to the first dose of study drug on C1D1.

               2. Limited-field radiotherapy ≤ 7 days or extended-field thoracic radiotherapy < 4
                  weeks of study drug on C1D1.

               3. Major surgery (excluding placement of vascular access) ≤ 4 weeks of the first
                  dose of study drug on C1D1.

          4. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except
             for alopecia and skin pigmentation.

          5. Have known or suspected brain metastases or spinal cord compression, unless the
             condition has been asymptomatic, treated with surgery and/or radiation, and has been
             stable without requiring escalating corticosteroids or anti-convulsant medications for
             at least four weeks prior to the first dose of study drug on C1D1.

          6. Prior therapy with CLN-081.

          7. Known hypersensitivity to CLN-081 or any drugs similar in structure or class.

          8. Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF)
             Class III/IV according to the New York Heart Association (NYHA) Functional
             Classification or serious cardiac arrhythmias requiring treatment.

          9. Mean resting corrected QT interval (QTc) > 470 msec obtained from three
             electrocardiograms (ECGs).

         10. Patient is unable to take drugs orally due to disorders or diseases that may affect
             gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease,
             ulcerative colitis) or malabsorption syndrome, or procedures that may affect
             gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.

         11. Have any condition or illness that, in the opinion of the investigator, might
             compromise patient safety or interfere with the evaluation of the safety of the drug.

         12. Pregnant or lactating women; women of child-bearing potential (WOCBP) must have a
             negative serum pregnancy test ≤ 7 days prior to receiving study drug on C1D1. WOCBP
             and males with partners of child-bearing potential must agree to use adequate birth
             control throughout their participation and for six months following the last dose of
             study treatment.

         13. History of another primary malignancy ≤ 2 years prior to starting study drug on C1D1,
             except for adequately treated basal or squamous cell carcinoma of the skin or cancer
             of the cervix in situ.

         14. Uncontrolled intercurrent illness including, but not limited to, uncompensated
             respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis
             B, hepatitis C, HIV, and active clinical tuberculosis), or renal transplant; ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric
             illness/social situations that would limit compliance with study requirements.

         15. Active bleeding disorders.

         16. Is, in the Investigator's opinion, unable or unwilling to comply with the trial
             procedures.