skb264 monotherapy in selected subjects with advanced solid tumors

Conditions: Selected Subjects with Advanced Solid Tumors

Summary: the purpose of this study is to assess the safety and efficacy of skb264 monotherapy in subjects with selected advanced solid tumors.the study is divided into two parts: the part ⅰ consists of 5 cohorts, and the part ⅱ for expansion. eligible subjects will receive skb264 monotherapy, until there is no longer clinical benefit, intolerable toxicity, discontinuation of study treatment required by the subject, or other protocol-specified treatment discontinuation criteria, whichever occurs first.

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.

Eligibility criteria:
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 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) ; 3. 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; 4. 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; 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 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; 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 on or after treatment, with prior therapies including platinum-based chemotherapy and anti-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 or cytology or hematology other than egfr-sensitive mutations ;②have failed targeted therapy for applicable genetic alterations or chemotherapy; 8. pd as assessed by imaging on or after the most recent treatment for locally advanced or metastatic disease; 9. ability to provide fresh or archival tumor tissue for biomarker testing and analysis. 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 of childbearing potential who use effective medical contraception during the study treatment 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 to comply with the protocol- specified visits and relevant procedures. exclusion criteria: 1. for nsclc, histologically or cytologically confirmed the presence of small cell lung cancer, neuroendocrine carcinoma, and carcinosarcoma components; 2. subjects with known meningeal metastases, brainstem metastases, spinal cord metastases 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 and cerebrovascular risk factors: 5. uncontrolled systemic disease as judged by the investigator: 6. 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; 7. clinically serious lung injuries caused by lung diseases, including but not limited to any underlying lung diseases or prior pneumonectomy; 8. presence of active chronic inflammatory bowel disease, gi tract obstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, or acute gi tract bleed; 9. 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; 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 known severe hypersensitivity to other monoclonal antibodies; 13. prior trop2-targeted therapy; 14. prior treatment with any drug therapy targeting topoisomerase i inhibitor, including antibody-drug conjugates (adcs); 15. major surgery within 4 weeks prior to the first dose or expected to require major surgery 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 small molecule tkis, nonspecific immunomodulatory therapy , and chinese patent drug preparations for approved anti-tumor indications within 2 weeks prior to the first dose; 18. 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; 19. live vaccines inoculated within 30 days prior to the first dose or planned to be inoculated during the study; 20. rapid deterioration of disease, such as significant changes in performance status during 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 or symptoms secondary to tumors that can lead to high medical risks and/or uncertainties in survival evaluation; 23. any condition that, in the opinion of the investigator, make the subject unsuitable for participation in this study.