Phase II Study of JS212/JS213 as Monotherapy and in Combination in Patients With Advanced Malignant Solid Tumors

Exclusion Criteria

• •1. Major surgery, radiotherapy, chemotherapy, immunotherapy or other anti-tumor therapy, or other investigational agents administered prior to the first study dose.
• •3. Presence of active central nervous system (CNS) metastases.
• •4. Presence of clinically significant pleural effusion, ascites, or pericardial effusion requiring repeated intervention.
• •5. Uncontrolled hypertension despite medical therapy, or history of hypertensive crisis or hypertensive encephalopathy.
• •6. Severe cardiovascular or cerebrovascular disease.
• •7. History of interstitial lung disease (ILD)/non-infectious pneumonitis requiring corticosteroid therapy.
• •8. Severe bone injury due to tumor bone metastasis as judged by the investigator.
• •9. Severe infection (CTCAE v5.0 \> Grade 2) within 28 days prior to the first study dose.
• •10. Active tuberculosis, hepatitis B, or hepatitis C infection.
• •11. History of immunodeficiency, or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• •12. History of another primary malignancy, except those with curative treatment and no known active disease for \>5 years and low potential risk of recurrence.
• •13. Known hypersensitivity or severe allergic reaction to the study treatment, any of its components, or excipients.
• •14. Presence of any other condition that may result in premature discontinuation from the study.
• •15. Diagnosis of any other malignancy within 5 years.
• •16. Subjects participating in Cohorts 1, 3, 4, and 5:Prior treatment with an ADC targeting EGFR and/or HER3, or prior treatment with an ADC utilizing a topoisomerase I inhibitor as the payload.
• •17. Subjects participating in Cohorts 2, 3, 4, and 5:Administration of any live or live-attenuated vaccine within 28 days prior to the first dose, or anticipated need for such vaccination during the study.Use of systemic corticosteroids or other immunosuppressive agents for ≥7 consecutive days within 14 days prior to the first dose.Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose.Development of a drug-related adverse event leading to permanent discontinuation of prior anti-PD-(L)1 antibody therapy.
• •18. Subjects participating in Cohorts 4:Imaging in the screening period demonstrates tumor encasement of major blood vessels, significant necrosis, or cavitation that, in the investigator's opinion, may confer a bleeding risk.Clinically significant hemoptysis or tumor bleeding of any cause within 28 days prior to the first dose.Gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months prior to enrollment, or current high risk of hollow organ perforation/fistula formation as judged by the investigator.History of gastrointestinal bleeding within 6 months prior to enrollment, or documented gastrointestinal bleeding tendency.Severe, non-healing or dehiscent wound, active ulcer, or untreated fracture.Significant bleeding diathesis or severe coagulopathy.Use of antiplatelet therapy or therapeutic anticoagulation within 14 days prior to the first dose.Development of a drug-related adverse event leading to permanent discontinuation of prior bevacizumab or similar agent therapy.