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

Inclusion Criteria:

1. Willing and able to provide signed and dated informed consent prior to any studyrelated procedures and willing and able to comply with all study procedures.
2. Patients with histologically or cytologically confirmed advanced solid tumor orrelapsed or refractory Non-Hodgkin Lymphoma (including but not limited to inert andtransformed type, patients with inert lymphoma must undergo systematic treatment atthe time of screening), which has progressed after treatment with standard therapiesor intolerant of standard therapies or have no standard of care.
3. Subject must have at least one measurable lesion by RECIST 1.1 or per Cheson criteria (Lugano 2014).
4. Subjects must be 18 years to 80 years of age at the time of screening.
5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Have life expectancy of at least 12 weeks based on investigator's judgement.
7. Sufficient organ and bone marrow functions before screening or administration.
8. Women of reproductive potential must have negative serum beta human chorionicgonadotropin (β -HCG) pregnancy test at the time of screening.
9. Women of reproductive potential who are sexually active must consistently use highlyeffective contraception/birth control (less than 1% per year) between signing of theinformed consent and 90 days after the last administration of the study drug.

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 withinthe 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 studydrug, 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 firstdose 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 fromprevious 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 otherclinical 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 4weeks before the first dose of study drug.
12. Known allergies to the active ingredient or excipients of the test drug, or history ofsevere allergic reaction (≥ grade 3) to any other monoclonal antibody or intravenoustherapeutic protein preparation drug.
13. History of interstitial lung disease or noninfectious pneumonia requiringcorticosteroid treatment.
14. More than moderate amount of uncontrollable pleural, abdominal or pericardial effusionrequiring repeated drainage or with obvious symptoms.
15. Subjects must not have an active autoimmune disease, a history of autoimmune diseaserequiring systemic therapy, or a history of autoimmune disease within 2 years of thefirst dose of study drug.
16. Clinically uncontrolled illness, including but not limited to severe diabetes,uncontrolled hypertension, serious endocrine disorders or other serious diseasesrequiring 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, hepatitisC, hepatitis B or active COVID-19 infection; previous or current active pulmonarytuberculosis and other active infectious diseases.
18. Severe infections requiring intravenous administration within 7 days before the firstdose 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 anginapectoris, congestive heart failure (NYHA grade ≥ II), valvular disease withsignificant clinical significance, and serious out of control arrhythmia requiringdrug 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 organtransplantation.
22. Any known mental illness or disorder, substance abuse history, drug abuse history oralcohol 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 participatingthe study.