Inclusion Criteria:

          1. Histologically or cytologically confirmed recurrent, metastatic NSCLC.

          2. Documented EGFR exon 20 insertion mutation demonstrated by a test routinely used by
             each institution and performed in a CLIA-certified or equivalent laboratory.

          3. Prior treatment in the recurrent/metastatic disease setting including:

               1. A platinum-based chemotherapy regimen (or other chemotherapy regimen if
                  platinum-based chemotherapy is contra-indicated)

               2. Any other approved standard therapy that is available to the patient, unless this
                  therapy is contraindicated, intolerable to the patient, or is declined by the
                  patient. In the case of a patient declining such therapy, documentation that the
                  patient has been informed and declined should be documented in the medical
                  record.

          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
             and comply with study procedures.

        Exclusion Criteria:

          1. Prior Exon 20 Patients Only

             a. No Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib,
             TAK788, tarloxotinib, JNJ-61186372).

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

             a. Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib,
             TAK788, tarloxotinib, JNJ-61186372).

          3. All Patients

             Treatment with any of the following:

               1. An EGFR tyrosine kinase inhibitors (TKIs) ≤ 8 days or 5x the terminal phase
                  elimination half-lives, whichever is longer, prior to the first dose of study
                  drug on C1D1

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

               3. Radiotherapy < 28 days and palliative radiation ≤ 14 days prior to the first dose
                  of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut
                  progression prior to to being eligible for evaluation as target lesions.

               4. Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.

               5. Major surgery (excluding placement of vascular access) ≤ 28 days 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. Patients with chronic, but stable Grade 2
             toxicities may be allowed to enroll after agreement between the Investigator and
             Sponsor.

          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. Past medical history of interstitial lung disease, drug-induced interstitial lung
             disease, radiation pneumonitis which required steroid treatment, or any evidence of
             clinically active interstitial lung disease.

         10. Resting corrected QT interval (QTc) > 470 msec.

         11. 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.

         12. 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.

         13. 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.

         14. 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.

         15. Uncontrolled intercurrent illness including, but not limited to, uncompensated
             respiratory, cardiac, hepatic, or renal disease, active infection (including 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.

         16. For patients with a history of hepatitis B, active infection as defined by a positive
             HBsAg test and detectable HBV DNA. Patients ineligible due to detectable levels of HBV
             DNA at baseline may be rescreened for enrollment if their HBV DNA levels become
             undetectable after treatment with antiviral agents, and upon agreement between the
             investigator and Sponsor.

         17. For patients with a history of hepatitis C, active infection as defined by a reactive
             HCV antibody test and detectable HCV RNA.

         18. Active bleeding disorders.

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