SKB264 Monotherapy in Selected Subjects With Advanced Solid Tumors

The second part of this study is a randomized, open-label, multicenter Phase 2 clinical study of SKB264 monotherapy versus docetaxel in subjects with locally advanced or metastatic non-squamous NSCLC.

Inclusion criteria

• Males or females aged ≥ 18 to ≤ 75 years at the time of signing the ICF;
• The following histologically or cytologically confirmed tumor types will be enrolled:

• Part Ⅰ Cohort 1, Cohort 2, Cohort 3, Cohort 5 and Part Ⅱ: histologically or cytologically confirmed Non Small Cell Lung Cancer (NSCLC);
• Part Ⅰ Cohort 4: histologically or cytologically confirmed nonkeratinizing differentiated or undifferentiated nasopharyngeal carcinoma (NPC) ;
• For subjects enrolled in Part I Cohort 1 and Part II, the following criteria must be met:①EGFR-sensitive mutations confirmed by tumor histology or cytology or hematology;②Failure of prior EGFR-TKI therapy and chemotherapy;
• For subjects enrolled in Part I Cohort 2, the following criteria must be met:①EGFR-sensitive mutations confirmed by tumor histology or cytology or hematology;②Failure of prior EGFR-TKI therapy;③No prior systemic therapy for locally advanced or metastatic NSCLC other than EGFR-TKI therapy;
• 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 fusion gene; ②Subjects must have met one of the following conditions for prior systemic therapy:A. Have received platinum-based chemotherapy in combination with anti-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/L1 monoclonal antibody (in either order) as the only prior second-line therapy;

• 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 on or after treatment, with prior therapies including platinum-based chemotherapy and anti-PD-1/PD-L1 monoclonal antibody therapy;

• 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 or cytology or hematology other than EGFR-sensitive mutations ;②have failed targeted therapy for applicable genetic alterations or chemotherapy;

• PD as assessed by imaging on or after the most recent treatment for locally advanced or metastatic disease;
• Ability to provide fresh or archival tumor tissue for biomarker testing and analysis.
• At least one measurable target lesion per RECIST 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Expected survival ≥ 12 weeks;
• Adequate organ and bone marrow function;
• Female subjects of childbearing potential and male subjects with partners of childbearing potential who use effective medical contraception during the study treatment period and for 6 months after the end of dosing;
• Subjects who voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol- specified visits and relevant procedures.

Exclusion criteria

• For NSCLC, histologically or cytologically confirmed the presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components;
• Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active brain metastases.
• Other malignancies within 3 years prior to the first dose;
• Presence of any cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors:
• Uncontrolled systemic disease as judged by the investigator:
• History of (noninfectious) interstitial pneumonia (ILD)/noninfectious pneumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis, or suspected ILD/noninfectious pneumonitis at screening that cannot be excluded by imaging;
• Clinically serious lung injuries caused by lung diseases, including but not limited to any underlying lung diseases or prior pneumonectomy;
• Presence of active chronic inflammatory bowel disease, GI tract obstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, or acute GI tract bleed;
• Toxicities treated by prior anti-tumor therapy having not recovered to ≤ Grade 1 (as per NCI CTCAE V5.0) or to the levels specified in the eligibility criteria;
• Presence of active hepatitis B or hepatitis C;
• Subjects with HIV test positive or history of AIDS; known active syphilis infection;
• Known allergy to the study drug or any of its components, and a history of known severe hypersensitivity to other monoclonal antibodies;
• Prior TROP2-targeted therapy;
• Prior treatment with any drug therapy targeting topoisomerase I inhibitor, including antibody-drug conjugates (ADCs);
• Major surgery within 4 weeks prior to the first dose or expected to require major surgery during the study;
• Systemic anti-infective therapy within 2 weeks prior to the first dose;
• Receipt of any systemic anti-tumor therapy such as macromolecular targeted therapy, immunotherapy, etc. within 4 weeks prior to the first dose; receipt of small molecule TKIs, nonspecific immunomodulatory therapy , and Chinese patent drug preparations for approved anti-tumor indications within 2 weeks prior to the first dose;
• Ongoing long-term systemic corticosteroid therapy of > 10 mg prednisone or equivalent dose of systemic corticosteroids or equivalent anti-inflammatory active medication or any form of immunosuppressive therapy prior to the first dose;
• Live vaccines inoculated within 30 days prior to the first dose or planned to be inoculated during the study;
• Rapid deterioration of disease, such as significant changes in performance status during the screening process prior to the first dose;
• Pregnant or lactating women;
• Presence of local or systemic diseases caused by non-malignancies; or diseases or symptoms secondary to tumors that can lead to high medical risks and/or uncertainties in survival evaluation;
• Any condition that, in the opinion of the investigator, make the subject unsuitable for participation in this study.