Study of YH004 (4-1BB Agonist Antibody) in Advanced Solid Tumors And Relapsed Or Refractory Non-Hodgkin Lymphoma

Exclusion Criteria

• •1. Previous exposure to an anti-CD137 (e.g., utomilumab, urelumab) antibodies.
• •2. Subjects must not have another active invasive malignancy within 2 years or currently.
• •3. Subjects have received any anticancer therapy or another investigational agent within the longer of 4 weeks or 5 half-lives before the first dose of the study drug.
• •4. Continuance of toxicities due to prior anti-tumor therapy that have not recovered to ≤ Grade 1 per CTCAE 5.0.
• •5. Subjects who have major operations within 4 weeks before the first dose of the study drug, or minor surgery within 2 weeks prior to the first dose.
• •6. Subjects have received any radiotherapy within the longer of 4 weeks before the first dose of the study drug.
• •7. Subjects with primary CNS malignancy or symptomatic CNS metastasis.
• •8. Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy or treatment discontinuation due to previous immunotherapy.
• •9. Subjects must not receive concurrent or prior use of an immunosuppressive agent within 4 weeks of the first dose of study drug.
• •10. Subjects must not receive any other investigational drug or participated in other clinical studies within 4 weeks before the first dose of study drug.
• •11. Subjects must not have received a live vaccine or attenuated live vaccine within 4 weeks before the first dose of study drug.
• •12. Known allergies to the active ingredient or excipients of the test drug, or history of severe allergic reaction (≥ grade 3) to any other monoclonal antibody or intravenous therapeutic protein preparation drug.
• •13. History of interstitial lung disease or noninfectious pneumonia requiring corticosteroid treatment.
• •14. More than moderate amount of uncontrollable pleural, abdominal or pericardial effusion requiring repeated drainage or with obvious symptoms.
• •15. Subjects must not have an active autoimmune disease, a history of autoimmune disease requiring systemic therapy, or a history of autoimmune disease within 2 years of the first dose of study drug.
• •16. Clinically uncontrolled illness, including but not limited to severe diabetes, uncontrolled hypertension, serious endocrine disorders or other serious diseases requiring systemic treatment such as severe abnormal thyroid function.
• •17. Subjects must not have a history or persistent active virus or tuberculosis infection. Including but not limited to: human immunodeficiency virus (HIV), syphilis, hepatitis C, hepatitis B or active COVID-19 infection; previous or current active pulmonary tuberculosis and other active infectious diseases.
• •18. Severe infections requiring intravenous administration within 7 days before the first dose of study drug.
• •19. Severe cerebro-cardiovascular disease within 6 months of the first dose of study drug, such as cerebrovascular rupture, stroke, myocardial infarction, unstable angina pectoris, congestive heart failure (NYHA grade ≥ II), valvular disease with significant clinical significance, and serious out of control arrhythmia requiring drug treatment (pulmonary hypertension or left ventricular ejection fraction (LVEF) ≤ 50% during screening period).
• •20. QTc \> 480 ms at baseline, corrected for heart rate using Frederica's formula.
• •21. Subjects must not have a history of allogeneic bone marrow transplantation or organ transplantation.
• •22. Any known mental illness or disorder, substance abuse history, drug abuse history or alcohol dependence history that would preclude subject from participation.
• •23. Females who are lactating, except for whom agreed to stop lactating during the trial.
• •24. Any condition that the investigator believes may not be appropriate for participating the study.