A Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-cluster Differentiation Antigen 47 (CD47) Monoclonal Antibody Injection (IBI188) in Patients With Advanced Malignant Tumors and Lymphomas

1. Able to understand and willing to sign the ICF.

2. Male or female subject above18 years.

3. Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors and lymphomas that are refractory to standard therapy, or for which no standard therapy exists.

4. For dose expansion at the RP2D: subject has measurable disease per RECIST v1.1. that was not in a prior radiation area within past 6 months, unless tumor growth was documented following radiation. Lymphomas have at least one measurable lesion and FDG-avid lesion according to the Lugano 2014 criteria.

5. Separate informed consent for subjects who provide archived tissue biopsies for biomarker testing (Optional).

6. ECOG Performance Status 0 to 1

7. Subjects with life expectancy of ≥ 3 month

8. No herbal/alternative medications within 14 days prior to the first dose of IBI188.

9. Must have adequate organ function, prior to start of IBI188, including the following:

1. Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L; Lymphocyte counts ≥ 0.5 x109/L

2. Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 X ULN (≤5 X ULN if with liver involvement)

3. Renal: serum creatinine ≤ 1.5 times the ULN or estimated creatinine clearance ≥50mL/min (Cockroft and Gault formula \[https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation\]).

4. Coagulation tests INR \< 2.0, activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN

10. Subjects (women of child-bearing potential and males) must be willing to use viable contraception method that is deemed effective by the investigator throughout the treatment period and for at least three months following the last dose of study drug. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.

11. Subjects who have had major surgery within the 28-days from the screening;

12. Subjects with idiopathic pulmonary fibrosis or unresolved active or chronic inflammatory pulmonary disease are excluded. Subjects with a history of radiation pneumonitis which has resolved are eligible.

13. Positive for human immunodeficiency virus (HIV) infection.

14. Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer\< 1000 cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled.

15. History of primary immunodeficiency, stem cell or organ transplant, or previous clinical diagnosis of tuberculosis disease.

16. Subject who have had severe infection deemed clinically significant per investigator within 4 weeks or signs and symptoms of any active infection within 2 weeks prior to the first dose administration.

17. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a history of any significant drug allergy (e.g., anaphylaxis, hepatotoxicity, immune-mediated thrombocytopenia or anemia).

18. Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who had to discontinue prior immunotherapy treatment due to irAEs of any grade.

19. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).

20. Any other serious underlying medical (e.g. uncontrolled diabetes mellitus, uncontrolled hypertension, active gastric ulcer, uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and clotting disorders), psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect subject compliance or place the subject at high risk from treatment-related complications.

21. Known history of hypersensitivity to any components of the IBI188 product.

What this study is about