SKB264 Monotherapy in Selected Subjects with Advanced Solid Tumors

Inclusion Criteria:

1. Males or females aged ≥ 18 to ≤ 75 years at the time of signing the ICF;

2. The following histologically or cytologically confirmed tumor types will beenrolled:

• Part Ⅰ Cohort 1, Cohort 2, Cohort 3, Cohort 5 and Part Ⅱ: histologically orcytologically confirmed Non Small Cell Lung Cancer (NSCLC);

• Part Ⅰ Cohort 4: histologically or cytologically confirmed nonkeratinizingdifferentiated or undifferentiated nasopharyngeal carcinoma (NPC) ;

3. For subjects enrolled in Part I Cohort 1 and Part II, the following criteria must bemet:①EGFR-sensitive mutations confirmed by tumor histology or cytology orhematology;②Failure of prior EGFR-TKI therapy and chemotherapy;

4. For subjects enrolled in Part I Cohort 2, the following criteria must bemet:①EGFR-sensitive mutations confirmed by tumor histology or cytology orhematology;②Failure of prior EGFR-TKI therapy;③No prior systemic therapy for locallyadvanced or metastatic NSCLC other than EGFR-TKI therapy;

5. For subjects enrolled in Part I Cohort 3, the following criteria must be met:

①NSCLC confirmed by tumor histology to be EGFR wild-type and negative for ALK fusiongene; ②Subjects must have met one of the following conditions for prior systemictherapy:A. Have received platinum-based chemotherapy in combination withanti-PD-1/L1 monoclonal antibody therapy as the only prior first-line therapy;B.Have received sequential treatment with platinum-based chemotherapy and anti-PD-1/L1monoclonal antibody (in either order) as the only prior second-line therapy;

6. For subjects enrolled in Part I Cohort 4, the following criteria must be met: Have received prior second-line or above systemic therapies and have progressed onor after treatment, with prior therapies including platinum-based chemotherapy andanti-PD-1/PD-L1 monoclonal antibody therapy;

7. For subjects enrolled in Part I Cohort 5, the following criteria must be met:

①The presence of other driver gene alterations confirmed by tumor histology orcytology or hematology other than EGFR-sensitive mutations ;②have failed targetedtherapy for applicable genetic alterations or chemotherapy;

8. PD as assessed by imaging on or after the most recent treatment for locally advancedor metastatic disease;

9. Ability to provide fresh or archival tumor tissue for biomarker testing andanalysis.

10. At least one measurable target lesion per RECIST 1.1;

11. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;

12. Expected survival ≥ 12 weeks;

13. Adequate organ and bone marrow function;

14. Female subjects of childbearing potential and male subjects with partners ofchildbearing potential who use effective medical contraception during the studytreatment period and for 6 months after the end of dosing;

15. Subjects who voluntarily participate in the study, sign the ICF, and will be able tocomply with the protocol- specified visits and relevant procedures.

Exclusion Criteria:

1. For NSCLC, histologically or cytologically confirmed the presence of small cell lungcancer, neuroendocrine carcinoma, and carcinosarcoma components;

2. Subjects with known meningeal metastases, brainstem metastases, spinal cordmetastases and/or compression, or active brain metastases.

3. Other malignancies within 3 years prior to the first dose;

4. Presence of any cardiovascular and cerebrovascular diseases or cardiovascular andcerebrovascular risk factors:

5. Uncontrolled systemic disease as judged by the investigator:

6. History of (noninfectious) interstitial pneumonia (ILD)/noninfectious pneumonitisrequiring steroid therapy and current ILD/noninfectious pneumonitis, or suspectedILD/noninfectious pneumonitis at screening that cannot be excluded by imaging;

7. Clinically serious lung injuries caused by lung diseases, including but not limitedto any underlying lung diseases or prior pneumonectomy;

8. Presence of active chronic inflammatory bowel disease, GI tract obstruction, severeulcers, gastrointestinal perforation, abdominal abscess, or acute GI tract bleed;

9. Toxicities treated by prior anti-tumor therapy having not recovered to ≤ Grade 1 (asper NCI CTCAE V5.0) or to the levels specified in the eligibility criteria;

10. Presence of active hepatitis B or hepatitis C;

11. Subjects with HIV test positive or history of AIDS; known active syphilis infection;

12. Known allergy to the study drug or any of its components, and a history of knownsevere hypersensitivity to other monoclonal antibodies;

13. Prior TROP2-targeted therapy;

14. Prior treatment with any drug therapy targeting topoisomerase I inhibitor, includingantibody-drug conjugates (ADCs);

15. Major surgery within 4 weeks prior to the first dose or expected to require majorsurgery during the study;

16. Systemic anti-infective therapy within 2 weeks prior to the first dose;

17. Receipt of any systemic anti-tumor therapy such as macromolecular targeted therapy,immunotherapy, etc. within 4 weeks prior to the first dose; receipt of smallmolecule TKIs, nonspecific immunomodulatory therapy , and Chinese patent drugpreparations for approved anti-tumor indications within 2 weeks prior to the firstdose;

18. Ongoing long-term systemic corticosteroid therapy of > 10 mg prednisone orequivalent dose of systemic corticosteroids or equivalent anti-inflammatory activemedication or any form of immunosuppressive therapy prior to the first dose;

19. Live vaccines inoculated within 30 days prior to the first dose or planned to beinoculated during the study;

20. Rapid deterioration of disease, such as significant changes in performance statusduring the screening process prior to the first dose;

21. Pregnant or lactating women;

22. Presence of local or systemic diseases caused by non-malignancies; or diseases orsymptoms secondary to tumors that can lead to high medical risks and/oruncertainties in survival evaluation;

23. Any condition that, in the opinion of the investigator, make the subject unsuitablefor participation in this study.