AP-L1898 Capsule in Patients With Non-small Cell Lung Cancer

Exclusion Criteria

• •1. Use of any chemotherapeutic agen within 14 days prior to the first dose of AP-L1898; or the time from discontinuation of other investigational product to the use of anticancer drug less than 5 half-lives or 28 days, whichever is shorter;
• •2. EGFR exon 20 insertion cohort in efficacy-extension stage: once used the drugs targeting EGFR exon 20 insertion mutation (e.g., AZD9291, TAK-788, Poziotinib, CLN-081, JNJ-372, etc.); the patients previously receiving AZD9291 for treatment of EGFR sensitive mutation are allowed to be enrolled;
• •3. Ongoing use of CYP3A potent inhibitor or inducer, or discontinuation of potent inhibitor less than 5 half-lives of the drug, or discontinuation of potent inducer less than 5 half-lives of the drug or 14 days (whichever is longer) at the first dose of AP-L1898;
• •4. Not recovered from the adverse event induced by previous antitumor therapy at screening (recovered to ≤ grade 1) (except alopecia);
• •5. Having other malignant tumors within 5 years prior to the start of treatment or simultaneously (except radically treated non-melanoma without evidence on recurrence of disease, including skin basal cell carcinoma or squamous cell carcinoma, breast/cervical carcinoma in situ, superficial bladder cancer and other carcinomas in situ);
• •6. Presence of active gastrointestinal disease or other conditions that may obviously affect absorption, metabolism or excretion of drugs;
• •7. Patients who known to have received organ transplantation;
• •8. Major surgery performed within 28 days prior to the first dose. Small surgery permitted, e.g., minimally invasive biopsy;
• •9. Patents with carcinomatous meningitis, spinal cord compression at present;
• •10. At rested state, mean corrected QT interval QTc, using Fridericia's correction formula\>450 ms in man or \>470 ms in woman on electrocardiography (ECG) (repeated for three times). A variety of clinically significant abnormalities in cardiac rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, degree III heart block, degree II heart block, PR interval\>250 ms. Any factors that may increase the risk of prolonged QTc interval or risk of arrhythmic events, e.g., heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in lineal relatives, or ongoing use of any drug known to prolong QT interval;
• •11. History of poorly controlled hypertension;
• •12. Previous history of the following diseases: interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, active interstitial lung disease with clinical evidence;
• •13. Patients with active brain metastasis, if the CNS metastasis is only limited to supratentorial area or cerebellum that has been adequately treated (surgery or radiotherapy) and radiologically stable for at least 4 weeks, and no corticosteroid is needed to control symptoms, the patients will be allowed to be enrolled;
• •14. In acute infection phase and requiring pharmacotherapy;
• •15. HBV DNA≥103 copies/mL or ≥200 IU/mL when the hepatitis B surface antigen is positive or hepatitis B core antibody is positive;
• •16. HCV-RNA \> the upper limit of reference at the site when hepatitis C antibody is positive;
• •17. Human immunodeficiency virus (HIV) antibody positive;
• •18. Patient with a previous history of clear mental disorder and taking drugs for treatment;
• •19. Patient with a history of drug abuse or drug taking;
• •20. Pregnant or lactating women;
• •21. Presence of other factors that may possibly affect the study results, interfere with their participation in the entire study, including previous or current physical condition (e.g., ocular disease, including corneal ulcer, conjunctivitis, etc.), treatment or laboratory examination abnormality, unwillingness to comply with each procedure, restriction and requirement in the study, as considered by investigators.