A Phase I Clinical Study of JS004 in Subjects With Recurrent/Refractory Malignant Lymphoma of China

Inclusion Criteria: 1.Able to understand and sign informed consent voluntarily 2.18-70 years old 3.Pathologically confirmed malignant lymphoma 4.ECOG PS: 0-1 5.Expected survival ≥12 weeks 6.At least one measurable lesion per Lugano response critieria 2014 for Lymphoma 7.Adequate organ and marrow function, as defined below: ANC≥1.5×109/L; PLT≥100×109/L and ≥75×109/L for subjects with bone marrow involvement; Hb≥90 g/L; TBIL≤1.5 ULN, ≤2 ULN in those with hep109atic metastasis, except subjects with documented Gilbert's syndrome who must have a baseline conjugated bilirubin ≤3.0 mg/dL; AST and ALT≤2.5 ULN, ≤5 ULN in those with hepatic metastasis; Cr≤1.5 UL, or creatinine clearance≥50mL/min for subject; INR ≤2 ULN and aPTT≤1.5×ULN for those with no prior anticoagulant therapy. 8.According to Fridericia's principle, QTC results need to match : Male≤450 ms，Female≤470 ms 9.Females of childbearing potential need to use effective contraception Exclusion Criteria: 1. Patients with known allergy to macromolecular protein preparations or JS004 components 2. Prior exposure to anti-BTLA or anti-HVEM antibodies 3. Enrolled in other clinical studies within 4 weeks prior to the first dose of study treatment 4. Major surgery within 4 weeks prior to the first dose of study treatmentor still recovering from prior surgery 5. Patients who discontinued previous immunotherapy due to immune-related adverse reactions 6. Immunosuppressive agents have been used within 4 weeks prior to the first dose of study treatment 7. Prior allogeneic bone marrow transplantation or solid organ transplantation 8. Live attenuated vaccine be administered 30 days before the first dose of study treatment 9. Two or more malignancies developed within 5 years prior to first dose of study treatment 10. The patients have symptomatic, untreated, or requiring ongoing treatment central nervous system (CNS) metastases 11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia.Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor. 12. Autoimmune disease within the previous 2 years 13. A history of rapid allergic reaction, eczema, or asthma beyond the control of topical corticosteroids 14. A history of primary immunodeficiency 15. Concomitant disease that is not under control, including but not limited to: persistent or active infection, unexplained fever \> 38.5°C, or heart disease, active peptic ulcer disease or gastritis 16. A history of active inflammatory bowel disease 17. HIV(+) 18. Patients with evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 19. Pregnant or lactating woman 20. Patients with vitiligo, alopecia, and hormonal replacement therapy have controlled endocrine defects 21. Any other medical factors that may affect subjects' rights, safety, compliance, ability to sign informed consent, and interpretation of study results. 22. Have a history of psychotropic drug abuse and unable to withdraw or have mental disorders.