Inclusion Criteria
1. Be able to understand and be willing to sign informed consent.
2. Male or female aged ≥ 18 years old at the time of signing informed consent.
3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC, who is not suitable for radical surgery or radiotherapy.
4. Documented EGFR mutations known to be associated with EGFR-TKI sensitivity, including Ex19del or L858R. Except for EGFR-TKI sensitive mutation, coexisting with other EGFR mutation types such as T790M can be allowed.
5. Prior systemic antitumor therapy allowed are listed as follows:
* Cohort 1: Subjects who are on the treatment of Furmonertinib as the first-line treatment setting.
* Cohort 2: Subjects failed in third-generation EGFR-TKI treatment and also failed in or were intolerant to 1-2 lines of chemotherapy.
* Cohort 3: subjects who haven't accepted any systemic therapy before. Prior adjuvant or neoadjuvant chemotherapy is permitted if an interval from the lost dose of adjuvant or neoadjuvant chemotherapy to the first documented PD is \>6 months.
6. Measurable lesions at baseline according to RECIST 1.1 criteria.
7. Has an ECOG performance status of 0 or 1.
8. Estimated life expectancy is more than 3 months.
9. Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to the first dose of study treatment/randomization.
Exclusion Criteria
1. Have experienced major surgical procedures or major trauma within 28 days prior to the first dose of study treatment/randomization.
2. Have received the following prior systemic antitumor therapy:
* Cohort 1: Have received chemotherapy, target therapy besides Furmonertinib, immunotherapy, biological therapy, and other antitumor drugs.
* Cohort 2: Have received chemotherapy, targeted therapy, immunotherapy, biological therapy, and other antitumor drugs within 28 days prior to the first dose of study treatment.
* Cohort 3: Have received systemic antitumor therapy for locally-advanced or metastatic NSCLC including chemotherapy, target therapy, immunotherapy, biotherapy, etc.
3. Cohort 2 only： Presence of other gene mutations, including ALK mutation, MET amplification, HER2 amplification, RAS mutation, etc. after progression on prior third-generation EGFR-TKI treatment.
4. Cohort 3 only：Has received the treatment of EGFR-TKI。
5. Prior FAK inhibitors treatment.
6. Have received systemic administration of potent inhibitors/inducers of CYP3A4, or P-gp inhibitors within 14 days prior to the first dose of treatment/randomization or are expected to receive systemic administration of these drugs during study treatment.
7. Has received radiotherapy for study disease or radiotherapeutic area covered for more than 30% of the bone marrow within 28 days prior to the first dose of study treatment/randomization.
8. Has had interstitial lung disease (ILD), drug-induced ILD, radiation pneumonia requiring steroid therapy; or diagnosis of clinically active ILD during the screening period.
9. Has a prior history of other malignancy within 3 years prior to signing informed consent.
10. Has known symptoms of spinal cord compression, active central nervous system (CNS) metastases, and/or carcinomatous meningitis.
11. Has a history of severe cardiovascular or cerebrovascular diseases within 6 months prior to the first dose of study treatment/randomization.
12. Has known uncontrollable pleural effusion, pericardial effusion, and ascites.
13. Has hemoptysis within 1 month prior to the first dose of study treatment/randomization with a blood volume of ≥2.5 mL every time or expected to require continuous hemostasis therapy during the study treatment.
14. Has active infections that are poorly controlled by systemic treatment.
15. Has active tuberculosis.
16. Known allergy, hypersensitivity or intolerance to IN10018 and/or third-generation EGFR-TKI, or their ingredients.
17. Pregnant or lactating women.
