ILKN421H Plus Pembrolizumab in Advanced Non-Small Cell Lung Cancer

To be enrolled in this study, participants must meet all the following inclusion criteria: 1. Provide written informed consent after full understanding of the study. 2. Adults at least 18 years of age. 3. ECOG performance status of 0 or 1. 4. Life expectancy ≥12 weeks. 5. At least one measurable lesion per iRECIST/RECIST 1.1 criteria, defined as: Lymph node lesion with short axis ≥1.5 cm or non-lymph node lesion with longest diameter ≥1 cm on CT/MRI; If the only lesion has undergone prior local treatment (radiotherapy, ablation, vascular intervention, etc.), there must be clear imaging evidence of disease progression in this lesion after local treatment. 6. Participants must have locally advanced or metastatic NSCLC, confirmed by available pathology records or current biopsy, that is advanced (non-resectable), or recurrent, for which no alternative, curative standard therapy exists. For Cohort 1 and Cohort 2, pathologically or cytologically confirmed advanced malignant locally advanced or metastatic NSCLC participants who have failed standard PD-1/L1 inhibitor alone or in combination with standard chemotherapy treatment regardless of PD-L1 expression. For Cohort 3 and Cohort 4, participants with pathologically or cytologically confirmed advanced, non-resectable locally advanced or metastatic NSCLC, who have previously untreated with any anticancer drugs expressing PD-L1 (TPS≥ 1%) as determined by an FDA-approved test. 7. Adequate organ and marrow function within 7 days before first dose, as defined below: 1. Absolute neutrophil count (ANC) ≥1.5×10⁹/L 2. Platelets (PLT) ≥100×10⁹/L 3. Hemoglobin (HGB) ≥90 g/L 4. Alanine aminotransferase (ALT) ≤2.5×ULN (≤5×ULN if known liver involvement) 5. Aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if known liver involvement) 6. Total bilirubin (TBIL) ≤1.5×ULN (≤3.0×ULN if diagnosed with Gilbert's syndrome) 7. Serum creatinine ≤1.5×ULN or estimated glomerular filtration rate (eGFR, calculated by Cockcroft-Gault formula or 24-hour urine measurement) ≥40 mL/min 8. International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN No component blood transfusion within 14 days prior to the above testing, and no supportive treatments (e.g., G-CSF, TPO, TPO receptor agonists, IL-11, EPO) within 7 days of above testing. 8. For Cohort 1 and Cohort 2, prior anti-tumor treatment-related toxicities resolved to ≤ Grade 1 (excluding Grade 2 neurotoxicity, Grade 2 hypothyroidism, any grade alopecia and pigmentation, and Grade 2 AEs that cannot resolve to ≤Grade 1 but remain stable long-term as judged by the investigator based on clinical practice; laboratory parameters refer to Inclusion Criteria 7). 9. Willing and able to comply with study schedules and all protocol requirements. 10. Women must meet one of the following criteria: postmenopausal for at least 24 consecutive months; surgically incapable of bearing children (i.e., have had a hysterectomy or bilateral oophorectomy); or utilizing a reliable form of contraception (either medication \[oral, implant, or injection\] or a barrier method). In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the participant to use a reliable form of contraceptive during the study Treatment Period and for at least 70 days following the last dose of study drug (Appendix IV). Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product; and Men must agree to the use of contraception during the study Treatment Period and for at least 180 days after the last dose of study drug.

To be included in this study, participants must not meet any of the following