A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AST2303 Tablets (ABK3376 Tablets) in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Exclusion Criteria

• •1. Previously received antitumor therapy targeting the c797s mutation
• •2. Carry any other known driver gene alterations
• •3. Have received any systemic anti-tumor treatment (including anti-tumor drugs in clinical research stage) within 2 weeks before the first administration or within 5 half lives of the drug (whichever is longer); Or receiving anti-tumor drugs with long half-life, such as immune checkpoint inhibitors, within 4 weeks before the first administration; Or received cytotoxic drugs with significant delayed toxicity, such as mitomycin C, within 6 weeks before the first administration;
• •4. Have received non-specific immunomodulatory agents, traditional Chinese medicine or traditional Chinese medicine preparations with approved anti-tumor indications within 2 weeks before the first administration
• •5. Strong inhibitors of CYP3A, P-gp or BCRP were used within 7 days before the first administration, or strong inducers of CYP3A, P-gp or BCRP were used within 3 weeks
• •6. Local (non bone lesions) radiotherapy within 4 weeks before the first dose, or bone radiotherapy within 2 weeks before the first dose;
• •7. Other malignant tumors besides the primary tumor
• •8. Subjects known to have meningeal metastasis, brainstem metastasis, spinal cord metastasis and / or compression, active brain metastasis. For brain metastasis subjects who have received local treatment in the past, if they are clinically stable for at least 4 weeks before the first administration of study treatment and do not need to use glucocorticoids or anticonvulsants for at least 14 days before the first administration of study treatment, they can participate in the study
• •9. The tumor invades the surrounding important organs and blood vessels or has the risk of esophago tracheal fistula or esophago pleural fistula
• •10. The toxicity of previous anti-tumor treatment has not returned to grade ≤ 1 (NCI CTCAE version 5.0 evaluation), except for grade ≤ 2 alopecia and peripheral neuropathy
• •11. Presence of cardiovascular and cerebrovascular disease or cardiovascular and cerebrovascular risk factors
• •12. Uncontrollable systemic diseases
• •13. There is a history of (non infectious) interstitial lung disease (ILD) or non infectious pneumonia requiring steroid treatment; Currently have ILD or non infectious pneumonia; Suspected ILD or noninfectious pneumonia that could not be excluded by imaging examination was present at screening
• •14. Pulmonary complications lead to clinically serious lung damage, including but not limited to the following: A. any underlying lung disease; b. Any autoimmune, connective tissue or inflammatory disease that may involve the lungs; c. Previous unilateral pneumonectomy
• •15. Severe acute or chronic infection
• •16. Being under long-term systemic corticosteroid treatment with prednisone \> 10 mg/ day or equivalent anti-inflammatory active drugs or any form of immunosuppressive treatment before the first administration. Subjects who need to use bronchodilators, inhaled or topical steroids or local steroid injections for treatment or as preventive medication for hypersensitivity reactions (such as medication before CT examination, etc.) can be included in the study
• •17. Subjects who had undergone major surgery within 4 weeks before the first dose or were expected to undergo major surgery during the study period
• •18. Bleeding symptoms with significant clinical significance or obvious bleeding tendency within 4 weeks before the first administration, such as gastrointestinal bleeding, gastric ulcer bleeding, active hemoptysis, etc
• •19. It is known that there are serious gastrointestinal dysfunction: such as untreated recurrent diarrhea, moderate to severe atrophic gastritis, gastrointestinal obstruction, Crohn's disease, ulcerative colitis, gastrointestinal perforation, etc
• •20. Known to have a history of hypersensitivity to the ingredients of the preparation used in the test
• •21. Pregnant or lactating women or women planning to become pregnant during the study
• •22. In the judgment of the investigator, the subject has other factors that may affect the results of the study or cause the forced termination of the study, such as alcohol abuse, drug abuse, suffering from other serious diseases (including mental diseases) requiring combined treatment, serious abnormal laboratory test values, family or social factors and other conditions that may affect the safety of the subject or the collection of test data, etc