H002 in Patients With EGFR Mutation Locally Advanced or Metastatic NSCLC

Inclusion Criteria:

1. Males or females aged ≥ 18 years at time of signing informed consent form (ICF).
2. Histological or cytological confirmed diagnosis of unresectable locally advanced ormetastatic NSCLC.
3. Subjects must have NSCLC harboring one or more active EGFR mutations known to beassociated with EGFR-TKI sensitivity (including, but not limited to Del19 and L858R).

• Part A: All subjects may provide tumor sample to central laboratory to analyzethe EGFR mutation status according to their own willingness;
• Part B: All subjects must provide tumor sample to central laboratory to analyzethe EGFR mutation status. And subjects must have NSCLC harboring EGFR C797Smutation. Note: Tumor sample can be either an archival sample or a sample obtained bypretreatment biopsy prior to H002 treatment.

4. • Part A: Subjects have received the best treatment available as determined by thephysician and must have radiological documented disease progression on the lasttreatment administered prior to enrolling in the study. • Part B: Subjects have received at least one previous EGFR-TKI treatment and haveradiological documented disease progression on the previous continuous EGFR-TKItreatment. In addition, subjects may have received other antitumor treatments and musthave radiological documented disease progression on the last treatment administeredprior to enrolling in the study.
5. Presence of at least one measurable lesion according to RECIST v1.1 per investigatorassessment.
6. ECOG performance status of 0-1.
7. Life expectancy ≥ 12 weeks.
8. Adequate hematologic and organ function per protocol.
9. Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must usehighly effective contraception per protocol throughout the study. WOCBP must have anegative serum and/or urine pregnancy test result within 7 days prior to the firstdose of H002.
10. Signed ICF, and this must be obtained before the performance of any protocol-specificprocedures.

Exclusion Criteria:

1. Treatment with any of the following: Prior treatment with an EGFR-TKI within 8 days or approximately 5 × t1/2 prior to thefirst dose of H002, whichever is longer; Prior treatment with immunotherapy orbiotherapy within 4 weeks prior to the first dose of H002; Radiotherapy (palliativeradiotherapy is completed at least 2 weeks prior to the first dose of H002 can beenrolled) within 4 weeks prior to the first dose of H002; Herbal therapy that hasanti-tumor effects within 2 weeks prior to the first dose of H002; Mitomycin andnitrosourea within 6 weeks prior to the first dose of H002; Oral fluorouracil such astegafur and capecitabine within 2 weeks prior to the first dose of H002; Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or other anti-tumordrugs for the treatment of NSCLC within 4 weeks or approximately 5 × t1/2 prior to thefirst dose of H002, whichever is longer.
2. Subjects with EGFR exon 20 insertion mutations only.
3. Prior marketed and/or investigational treatment for EGFR C797S mutation (including,but not limited to BTP-661411, TQB3804 and BLU-945).
4. Is currently participating and receiving investigational therapy or using aninvestigational device, or has participated in a study of an investigational agent andreceived study therapy or used an investigational device within 4 weeks or 5 × t1/2 ofthe investigational product, whichever is longer, prior to the first dose of H002.
5. Is expected to require any other form of anti-tumor therapy while on study.
6. Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy.
7. ≥ CTCAE v5.0 Grade 2 skin toxicity at screening.
8. Treatment with strong inhibitors and strong inducers of CYP3A4 within 2 weeks prior tothe first dose of H002, or anticipation of need for such drugs during study treatment.
9. Uncontrollable pleural effusion, ascites, or pericardial effusion.
10. Subjects who have symptomatic brain metastases, meningeal metastasis or spinal cordcompression.
11. Subjects who have a chronic or active infection that required systemic treatmentwithin 2 weeks prior to the first dose of H002.
12. Subjects who have gastrointestinal disorders that will affect oral administration orthe investigator judges that the absorption of H002 will be interfered.
13. History of hypersensitivity to active or inactive excipients of H002 or drugs with asimilar chemical structure or class to H002.
14. Subjects who received a diagnosis of, and/or tested positive at screening for humanimmunodeficiency virus (HIV).
15. Subjects with active hepatitis B.
16. Presence or history of malignancy other than NSCLC with the exception of some certainearly-stage cancers.
17. Subjects who have clinically significant cardiovascular diseases that occurred within 6 months prior to the first dose of H002, include but not limited to QTc interval ≥ 450 msec (male) or ≥ 470 msec (female).
18. Major surgery or significant traumatic injury occurring within 4 weeks prior to thefirst dose of H002 or anticipation of need for a major surgery during the study.
19. Medical history of ILD.
20. Medical history of severe eye disease without recovery to CTCAE v5.0 Grade 0 or 1.
21. Severe gastrointestinal disease within 4 weeks prior to the first dose of H002 and didnot recover to ≤ CTCAE v5.0 Grade 2.
22. Has any bleeding tendency or coagulopathy within 6 months prior to the first dose ofH002.
23. Administration of a live, attenuated vaccine within 4 weeks prior to the first dose ofH002 or anticipation of need for such a vaccine during the study.
24. Female subjects in pregnancy or lactation.
25. Any other circumstances that would, in the investigator's judgment, prevent thesubject's participation in the clinical study due to safety concerns or compliancewith clinical study procedures.