A Study of LP-300 with Carboplatin and Pemetrexed in Never Smokers with Advanced Lung Adenocarcinoma

Inclusion Criteria:

1. Patients with confirmed histopathological diagnosis of inoperable advanced (StageIII or IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of thelung with specific actionable genomic alterations (e.g., mesenchymal epithelialtransition (MET) exon14 skipping mutations, anaplastic lymphoma kinase (ALK),epidermal growth factor receptor (EGFR), neurotrophic tyrosine receptor kinase (NTRK) fusions, etc.). If pathological or radiological findings are inconclusive fora diagnosis of primary adenocarcinoma of the lung, additional studies must beperformed to confirm primary lung versus metastatic adenocarcinoma. Patients with noknown actionable genomic alterations are ineligible to enroll in the study.

2. Locally advanced inoperable or metastatic lung cancer.

3. Patients must be never smokers: a never smoker is an adult who has never smoked, orwho has smoked less than 100 cigarettes (or equivalent in other products such asvapes, cigars, pipes, hookahs, and marijuana use) in his or her lifetime. Note: apatient with actionable genomic alteration(s) who is a former smoker may be enrolledif such a patient would ordinarily be treated with pemetrexed and carboplatincombination based on institutional standard clinical practice; consultation with thesponsor's Medical monitor would be required

4. Patients who have received systemic treatment with tyrosine kinase inhibitors (TKIs)for non-small cell lung cancer but have experienced disease progression,unacceptable TKI-related toxicities, or are unable to tolerate the further use ofTKIs.

5. Prior radiation therapy is allowed, provided (1) that at least one area ofmeasurable tumor (by computed tomography (CT) scan with at least one target lesion)per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has notbeen subject to prior irradiation, and (2) that any such therapy is completed andany radiation-induced sequelae are recovered at least 21 days before randomization.

6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0or 1.

7. Patients who are at least 18 years of age.

8. Patients with documented stable central nervous system (CNS) metastases with nocognitive deficits, or progressive sensory or motor deficits, or seizures during thelast 21 days prior to enrollment are eligible. Patients must have discontinuedanti-seizure medications and steroids at least 14 days prior to patient enrollment.

9. Patients must have fully recovered from any prior major surgical or diagnosticstaging procedure (e.g., thoracotomy, mediastinoscopy), and have a post-operativestatus of at least 30 days before enrollment.

10. Patients must have adequate bone marrow, adequate hepatic function, and baselinecreatinine levels documented by specific laboratory criteria within 21 days prior toenrollment, including the following:

• White blood cell count ≥ 2 x 10*9/L

• Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L

• Hemoglobin ≥ 10 g/dL

• Platelet count ≥ 100 x 10*9/L

• Total bilirubin < 1.5 x the upper limit of normal (ULN). For patients withGilbert's syndrome, total bilirubin < 2.5 x ULN

• Aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) ≤ 2.5 x ULN

• Alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5x ULN

• Alkaline phosphatase ≤ 2.5 x ULN

• Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L.

• Creatinine clearance ≥ 45 mL/min as calculated using the Cockcroft-Gaultmethodology (Cockcroft 1976)

• Magnesium ≥ 1.7 mg/dL

11. Female patients of child-bearing potential must have a negative pregnancy test andmust agree to use an acceptable contraceptive method during the study and for 12weeks after their last dose of study treatment. Male patients with partners ofchild-bearing potential must also agree to use an adequate method of contraceptionfor the duration of the study and for 12 weeks after their last dose of studytreatment. Note: a) A patient is considered of childbearing potential if she is biologicallycapable of having children and is sexually active. Medically acceptablecontraceptives include: (1) surgical sterilization (such as a tubal ligation,hysterectomy, or vasectomy), (2) approved hormonal contraceptives (such as birthcontrol pills, patches, implants or injections), (3) barrier methods (such as acondom or diaphragm) used with a spermicide (only if used in combination withanother mentioned method), or (4) an intrauterine device (IUD). Contraceptivemeasures and other medications sold for emergency use after unprotected sex, are notacceptable methods for routine use. If a female patient becomes pregnant, studytherapy must be discontinued immediately. Lastly, b) the period for use ofcontraception after last dose of pemetrexed or carboplatin should be determined bythe domestic drug labels and/or institutional standard clinical practice. For SKorea, contraception is to be used for 6 months after the last dose.

12. Patients must have been disease-free at least two years for other malignancies,excluding:

• Curatively-treated basal cell carcinoma,

• Ductal carcinoma in situ (DCIS) of the breast

• Non-melanomatous carcinoma of the skin, or

• Carcinoma in situ of the cervix.

13. Be willing to provide an archival tumor tissue sample, if available. The archivalsample must be from a tumor lesion that was not previously irradiated.Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Thesample must have been obtained less than 36 months prior to consent.

14. Provide signed, written, Institutional Review Board (IRB) approved informed consentprior to any screening procedures.

Exclusion Criteria:

1. Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma,or any form of mixed (e.g., small cell and adenocarcinoma or squamous andadenocarcinoma) histopathological diagnosis of primary lung cancer.

2. Patients with metastatic adenocarcinoma arising from any primary site other than thelung.

3. Patients who have received any prior investigational agents except forinvestigational TKI drugs. The minimum drug washout period for all TKIs, includingapproved and investigational, is ≥ 5 half-lives or 2 weeks, whichever is shorter.

4. Patients who have received chemotherapy and/or immunotherapy but transitioned to aTKI with no evidence of disease progression will be allowed to enroll. Patients whoexperienced disease progression while on chemotherapy and/or immunotherapy will beineligible for the trial.

5. Patients taking medications that are sensitive substrates of CYP2C19 or P-gptransporters

6. Patients with recent onset (within 6 months of randomization) of congestive heartfailure (New York Heart Association Classification Class II or greater), anginapectoris, unstable angina pectoris, serious uncontrolled cardiac arrhythmias,myocardial infarction, stroke, or transient ischemic attacks.

7. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of > 470msec. (average of triplicate ECGs) at Screening and/or on C1D1 (pre- dose) exceptfor a documented bundle branch block or unless secondary to pacemaker. In the caseof a documented bundle branch block or a pacemaker, discussion with the MedicalMonitor is required prior to enrollment.

8. Patients with unstable CNS metastases (characterized by progressive sensory/motorimpairment, cognitive/speech impairment, or seizure activity) within 21 days beforeenrollment.

9. Patients who do not have at least one (1) measurable disease site that has not beenpreviously irradiated.

10. Patients who are known to be positive for human immunodeficiency virus (HIV),hepatitis B virus surface antigen (HbsAg) or hepatitis C virus (HCV).

11. Patients with active infections, active interstitial lung disease, uncontrolled highblood pressure, uncontrolled diabetes mellitus, uncontrolled seizures (not due toCNS metastases) within the last 3 months, or other serious underlying medicalcondition.

12. Patients with documented hypersensitivity to any of the study medications (LP-300,pemetrexed, carboplatin and/or excipients) or supportive agents that may be used.

13. Patients who are pregnant or are breastfeeding.

14. Patients who have undergone blood transfusions within 10 days before randomization.

15. Any other medical intervention or other condition which, in the opinion of thePrincipal Investigator, could compromise adherence to study requirements or confoundthe interpretation of study results.

16. Patients who have a life expectancy of less than 3 months.