APG-2449 in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Dose exploration stage: non-small cell lung cancer diagnosed by histology and/orcytology and positive for ALK/ROS1 gene fusion (molecular diagnosis confirmed by theinvestigator) and malignant pleural mesothelioma, esophageal cancer and ovariancancer. Kind of patients with advanced tumors. Expansion stage: cohort 1, patients with non-small cell lung cancer who haveprogressed or are intolerant to TKI therapy, including patients withsecond-generation ALK TKI, or either ROS1 TKI, or third-generation ALK inhibitor (lorlatinib, etc.) with pFAK expression (pFAK expression is subject to centrallaboratory results) of about 10 or above; Cohort 2, TKI-naïve patients with ALK/ROS1fusion gene positive NSCLC. The molecular diagnosis results of the above patientscan be confirmed by the investigator.

2. ECOG Performance Status ≤ 1.

3. Expectation of life ≥ 3 months.

4. According to RECIST version 1.1, there is at least 1 measurable lesion.

5. Adequate hematologic and bone marrow functions.

6. Adequate renal and liver function.

7. Normal cardiac function.

8. Brain metastases with clinically controlled neurologic symptoms.

9. Serum pregnancy test results of women of childbearing age were negative within 7days before taking the first dose of study drug.

10. Men, women of childbearing age (postmenopausal women must have been menopausal forat least 12 months before they can be considered infertile) and their partnersvoluntarily take the study drug for at least 30 days after signing the informedconsent form and taking the study drug as deemed effective by the investigatorContraceptive measures

11. Ability to understand and willingness to sign a written informed consent form

12. Subjects must be willing and able to complete the research procedures and follow-upinspections.

13. Subjects are required to provide fresh (for recurrent subjects only) or archivedtumor tissue samples from within 28 days prior to treatment. If none of thesespecimens are available, they may be included after consultation with the sponsor.

14. Subjects should provide fresh biopsy tumor tissue specimens prior to treatment.

Exclusion Criteria:

1. Receiving concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy,biologic therapy); or any investigational therapy within 28 days prior to the firstdose of study drug.

2. Receiving TKI therapy within 8 days prior to the first dose of study drug.

3. Continuance of toxicities due to prior therapy that do not recover (CTCAE V5.0Grade> 1).

4. Has difficulty in swallowing, absorbing barrier, or other diseases blockingAPG-2449' taken.

5. Obvious cardiovascular disease history.

6. Failure to recover adequately, as judged by the investigator, from prior surgicalprocedures. Patients who have had major surgery within 28 days from study entry, andpatients who have had minor surgery within 14 days of study entry.

7. Active symptomatic fungal, bacterial and/or viral infection including, but notlimited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C).

8. Known allergies to study drug ingredients or their analogs.

9. Female subjects who are pregnant or breastfeeding, or expecting to become pregnantduring the study period.

10. According to the judgment of the investigator or sponsor, any symptoms or disease ofthe subject may endanger its safety or interfere with the safety assessment of thestudy drug.

11. Subjects who have used CYP3A4, CYP2C9, or CYP2C19 moderately potent inhibitors ormoderately potent inducers 1 week before receiving the study drug for the firsttime.

12. Subjects who used CYP3A4 substrates and narrow treatment window 1 week before thefirst study drug.