IMM2520, a PD-L1 and CD47 Bispecific Antibody in Patients With Advanced Solid Tumors

Exclusion Criteria

• •A subject meeting any of the following criteria must be excluded from the study.
• •1. Subjects are enrolled into another clinical study continuously, unless it is an observational, non-interfering clinical study or in the follow-up period of an interfering study.
• •2. Treatment with the last systemic chemotherapy within 3 weeks; treatment with hormone therapy and small-molecule target therapy within 2 weeks; palliative radiation treatment for non-target lesions within 2 weeks; treatment with non-specific immunomodulatory therapy within 2 weeks prior to the first administration.
• •3. Subjects with active central nervous system (CNS) metastases (Subjects with stable treated central nervous system \[CNS\] lesions who are off corticosteroid therapy for at least 2 weeks are not considered active).
• •4. Subjects who have received previous treatment with \> 1 PD-1 or PD-L1 inhibitors, such as pembrolizumab, nivolumab, atezolizumab or durvalumab.
• •5. Subjects who have received previous treatment with anti-CD47 monoclonal antibody fusion protein.
• •6. Subjects diagnosed with other malignancies within 2 years before the first dose with exceptions: a. cervical carcinoma in situ or basal or squamous cell carcinoma of the skin underwent radical resection; b. second primary carcinoma underwent radical resection and without recurrence within 5 years; c. double primary cancers that can benefit from this study in the opinion of the investigator.
• •7. Subjects who received prior allogeneic hematopoietic stem cell transplant or other organ transplants with acute or chromic GVHD（graft versus host disease） requiring the long-term immunosuppressive therapy before 6 months of treatment.
• •8. Subjects with active autoimmune diseases requiring systemic treatment (with glucocorticoids or immunosuppressive drugs) in the past 2 years with exceptions of hormone replacement therapy for thyroid disease, adrenal or pituitary insufficiency disease.
• •9. Concurrent medical condition requiring systemic corticosteroids (prednisone daily dose \> 20 mg or equivalent dose) within14 days prior to first dose of the investigational product.
• •10. Subjects who underwent a major surgery within 4 weeks prior to the first dose or planned to undergo a major surgery in 3 months after receiving the investigational drug (excluding catheterization, peripherally inserted central catheter, etc.).
• •11. Hypertension , pulmonary hypertension or unstable angina, which cannot be controlled by medication; treatment with myocardial infarction, bypass or stent surgery within 6 months prior to administration; a history of chronic heart failure rated by the New York Heart Association (NYHA) as grade 3-4; severe arrhythmia requiring treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia that, according to the judgment of the investigators, do not affect the study); QTcF \> 470 msec; history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to enrollment;
• •12. A history of arterial thrombosis, deep venous thrombosis and pulmonary embolism within 3 months prior to the first administration.
• •13. Subjects with diseases that may cause gastrointestinal bleeding or perforation;
• •14. Concurrent interstitial lung disease (ILD) (except for radiation therapy-induced loco regional interstitial pneumonia), severe chronic obstructive pulmonary disease, severe pulmonary insufficiency.
• •15. Subjects with thoracoabdominal or pericardial effusions that cannot be controlled by puncture and drainage and require repeated drainage or with significant symptoms.
• •16. Subjects with uncontrollable serious active infection (such as sepsis, bacteremia, and viremia) within 4 weeks before the first administration, or subjects with any signs or symptoms of active infection within 2 weeks, or subjects requiring antibiotic treatment within 2 weeks (except for the preventive application of antibiotics); fever of unknown cause \> 38.5℃ before the first dose (subjects with fever due to tumor can be included in the opinion of the subjects); active tuberculosis infection;
• •17. A known history of serious allergy to PD-1/PD-L antibodies.
• •18. Patients who received live attenuated vaccine within 4 weeks prior to the first dose of the investigational product, or plan to receive attenuated vaccine during the study.
• •19. Patients with human immunodeficiency virus (HIV) infection, hepatitis B surface antigen (HBsAg) positive at screening, and HBV-DNA above the lower limit of measurement; HCV antibody positive at screening and HCV-RNA above the lower limit of measurement.
• •20. Subjects with immune-related toxicity that leads to permanent drug discontinuation due to previous anti-tumor immunotherapy.
• •21. History of psychiatric illness or substance abuse is likely to interfere with the ability to comply with protocol requirements or giving informed consent.
• •22. Other situations where investigators believe they are inappropriate for participation in this study