AK112 in Non-squamous Non-small Cell Lung Cancer (NSCLC)Patients With Actionable Genomic Alterations (AGA) Who Have Failed to Previous Tyrosine Kinase Inhibitor (TKI) Treatment

Prior treatment

• Prior receipt of immunotherapy.
• Prior receipt of any systemic anti-tumor therapy for advanced-stage (IIIB-IV) NSCLC other than AGA-targeted TKIs.
• Concurrent participation in another clinical study, unless it is a non-interventional study or the follow-up phase of an interventional study.
• Receipt of AGA-targeted TKI therapy within 2 weeks prior to the first dose; receipt of non-specific immunomodulatory therapy within 2 weeks prior to the first dose.
• Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose.
• History of major medical conditions within 1 year prior to the first dose.

Other illness

• Imaging during the screening period shows tumor encasement of major blood vessels or significant necrosis/cavitation, and the investigator determines that study participation would pose a bleeding risk.
• History of malignancy other than NSCLC within 3 years prior to the first dose; participants with other malignancies that have been cured by local treatment are allowed.

Lab values

• AGA test report showing the presence of a common EGFR sensitizing mutation.

Other

• Histological or cytological pathology confirming the presence of a small-cell carcinoma component or a predominant squamous cell carcinoma component.
• Imaging during the screening period shows tumor invasion of surrounding vital organs or blood vessels.
• Central nervous system metastases: participants assessed by the investigator as not requiring local treatment may be eligible; leptomeningeal metastases are not eligible.

• Signed the Informed Consent Form (ICF) voluntarily。
• Participants must be aged between 18 and 75 years (inclusive), regardless of gender.
• ECOG performance status of 0 or 1.
• With a life expectancy of ≥3 months.
• Histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC.
• Prior to enrollment, participants must have at least one actionable genomic alteration (AGA) confirmed by tumor histology, cytology, or blood-based testing, including: EGFR, ALK, ROS1, NTRK, RET, BRAF and MET. Participants must provide a prior AGA test report; otherwise, AGA testing must be performed at the study site or at a site-designated laboratory before enrollment.
• Previous treatment failure with an AGA-targeted TKI.
• At least one measurable extracranial lesion as defined by RECIST v1.1.
• Adequate organ function confirmed.