This is a multicenter, open-label phase 2 study that will enroll KRASG12C mutated patients with locally advanced or metastatic NSCLC, receiving treatment (ABSK043 in combination with Glecirasib) in a 21-day combination cycle.

The study consists of an escalation part and an expansion part. The escalation part will evaluate the safety, tolerability, preliminary efficacy, and PK profile of different doses of ABSK043 in combination with Glecirasib, and the combination regimen recommended for the expansion part. The expansion part will further evaluate the safety, PK profile, and anti-tumor efficacy of ABSK043 in combination with Glecirasib at the one or more recommended dose (s).

Up to 86 patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) are planned to be enrolled in the study.

• Escalation Part: up to 50 previously treated patients with KRASG12C mutation.
• Expansion Part: up to 36 treatment-naïve patients with KRASG12C mutation.

Inclusion Criteria:

1. Prior to any protocol- specific procedures are performed, the patient should understand and voluntarily sign and date the written informed consent form.

2. Gender was not limited patients aged ≥18 years at the time of signing the informed consent.

3. Histologically or cytologically confirmed locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC).

   For patients in the dose-escalation cohort (Part A) of the escalation part:

   Patients must have experienced disease progression following at least one line of prior standard systemic therapy, but no more than two lines of systemic therapy.

   For patients in the dose confirmation cohort (Part B) of the escalation part :

   1. Prior treatment requirements for patients in cohort (Part B) are the same as those for patients in (Part A);
   2. Documented or central laboratory test report confirmed that the tumor was PD-L1 expression positive (≥1%) .

   For patients in the expansion cohort of the expansion part :

   1. Patients who have not received prior systemic therapy for locally advanced or unresectable/metastatic disease;
   2. Central laboratory test report confirmed that the tumor was PD-L1 expression positive (≥1%) .

4. Tumor tissue or blood test report confirmed KRASG12C mutation.

5. Patients must have at least one measurable lesion as defined by RECIST v1.1.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0~1.

7. Expected survival time of ≥3 months.

8. Patients must have adequate organ and bone marrow function.

Exclusion Criteria:

1. Histological or cytological evidence of small cell lung cancer or neuroendocrine carcinoma components.
2. Toxicities from prior antitumor therapy have not returned to baseline or stabilized.
3. Patients with active brain metastases.
4. The patient currently has active interstitial lung disease.
5. Patients currently have active autoimmune disease or a history of autoimmune disease that may be at risk for recurrence.
6. Any condition requiring systemic treatment with corticosteroids.
7. Uncontrolled or significant cardiovascular disease.
8. Has a known human immunodeficiency virus (HIV) infection that is not well controlled.
9. Any evidence of severe or uncontrolled diseases or other factors which in the Investigator's opinion makes it undesirable for the patients to participate in the study