A Phase 2 Study of ABSK043 Combined With Osimertinib

Inclusion Criteria：

1. Aged 18 or above, male or female.
2. Participants must understand and voluntarily participate in this study and must have been provided informed consent for study participation.
3. NSNLC confirmed by tissue or cytological pathology. NSCLC with a mixed histology is eligible, if adenocarcinoma is the predominant histology.
4. Diagnosed locally advanced or metastatic NSCLC
5. Different requirements for specific cohort:

   Dose escalation and backfill cohorts:
   1. Participants with disease in the adjuvant setting, post chemoradiotherapy setting, locally advanced stage or metastatic stage, who have received at least one prior line of third-generation EGFR-TKI-based monotherapy or combination therapy and experienced disease progression.
   2. Participants must have received ≥2 prior lines of frontline systemic therapy.
   3. Documented or central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
   4. Documented genetic testing report confirms the presence of EGFR alteration(s) in tumor or plasma.

   Expansion cohort(s):
   1. Participants must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting for locally advanced or metastatic disease.
   2. Central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
   3. Documented genetic testing reports confirm the presence of EGFR
6. Presence of at least one measurable tumor lesion
7. ECOG score 0-1 at screening.
8. The expected life expectancy after the first dose is \>12 weeks.

Exclusion Criteria:

* 1\. Histological or cytological examinations suggest that NSCLC squamous cells is the predominant histology, or contains small cell lung cancer, neuroendocrine carcinoma, etc.

  2\. Has a history of interstitial lung disease (ILD)/pneumonitis or active ILD 3. Spinal cord compression and unstable brain metastases. 4.Any unresolved toxicities from prior systemic therapy greater than CTCAE v6.0 Grade 1 at the time of starting study treatment.

  5\. Participants with obvious and unstable pleural effusion, peritoneal effusion or pericardial effusion .

  6\. Has a history of other malignant tumors, or currently have other malignant tumors.

  7\. Participants with known HIV infection.