A Study of MIL62 Combined With ICP-022 for the Treatment of R/R CD20+B Cell Lymphoma

Inclusion Criteria:

1. Age ≥18 years, gender not limited
2. Dose escalation phase: histologically confirmed CD20 positive B cell non-Hodgkin's lymphoma (except for chronic lymphocytic leukemia/small lymphocytic lymphoma); Expansion stage: R/R Follicular Lymphoma(FL): histologically confirmed CD20 positive grade 1-3a follicular lymphoma with no tissue transformation. In case of suspected clinical transformation, biopsy of the suspected site is required to confirm no transformation
3. Patients who have received at least one treatment regimen (with or without rituximab) without remission or progression after remission, or who are not tolerant to previous treatment
4. Except for the splenic marginal region lymphoma, there was at least one two-dimensional measurable lesion (CT scan or MRI), namely, the longest diameter of the lymph node lesion was >1.5cm, the shortest diameter was >1cm, and the longest diameter of the extra-junction lesion was >1cm.
5. Eastern cancer collaboration group(ECOG) physical status score: 0-2
6. Laboratory tests performed within 7 days prior to the first acceptance of the study drug met the following criteria: 1) platelet count ≥75 x 109/L, neutrophils ≥1.5 x 109/L, hemoglobin ≥9g/dL, if accompanied by bone marrow invasion, platelet ≥50×109/L, neutrophils absolute value ≥1.0×109/L;2) glutamic oxalacetic transaminase (AST) or glutamic-pyruvic transaminase (ALT) ≤ 2.5 x ULN;3) total bilirubin ≤ 1.5x Upper Limit of Normal(ULN); Renal creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault formula);4) prothrombin time (PT)/international normalized ratio(INR) ≤1.5 x ULN.
7. Expected survival ≥6 months
8. Sign a written informed consent.

Exclusion Criteria:

1. Received any of the following anti-tumor treatments before the first study drug: (1) received any monoclonal antibody within 3 months;(2) received chemotherapy within 28 days;(3) received anti-tumor Chinese (herbal) drug treatment within 28 days (2 doses or more);(4) received radiotherapy within 42 days;(5) received other anti-tumor treatment within 28 days, such as BTK kinase inhibitor, Phosphatidylinositol -3- hydroxykinase(PI3K) inhibitor treatment;6. Received obinutuzumab (Gazyva, GA101) treatment within 12 months;
2. Previous use of any anticancer vaccine
3. Patients who had received hematopoietic stem cell transplantation within 3 months before the first administration or who planned to receive hematopoietic stem cell transplantation within 3 months
4. Patients scheduled for major surgery within 28 days prior to initial administration or during the expected study period, except for diagnostic surgery
5. Participated in other clinical trials within 28 days prior to first receiving the drug under study, or plan to participate in other clinical trials at the same time as this study
6. Receiving prednisone treatment ≥20mg/ day or other corticosteroid treatment with the same dose as prednisone (if the dose can be kept stable below the dose level within 7 days before the baseline CT examination (<20mg/ day can be included);Patients who require warfarin or an equivalent vitamin K antagonist;
7. During the study period, drugs with moderate or severe inhibition or strong induction of cytochrome CYP3A4 were taken together
8. Subject has a history of any of the following diseases: central nervous system lymphoma or leukemia; Had other malignant tumors in the past 3 years, except basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that had received radical treatment;(3) progressive multifocal leukoencephalopathy (PML);(4) a history of stroke or intracranial hemorrhage within 6 months prior to receiving the study drug for the first time; Serious hemorrhagic diseases such as hemophilia A, hemophilia B, von Willebrand disease or spontaneous bleeding requiring blood transfusion or other medical intervention;
9. Patients with active bacteria, viruses, fungi, mycobacteria, parasites or other infections (excluding nail bed fungal infections) and requiring intravenous antibiotic treatment before enrollment
10. Impact testing scheme compliance or other serious results explain the poor control of the merger of the disease, including the clinical significance of cardiovascular disease (such as New York heart association class III or IV heart disease, myocardial within the past 6 months, obstruction or unstable type of arrhythmia, or unstable angina) or lung disease (including obstructive pulmonary disease (COPD) and history of bronchospasm);
11. Toxicity of any previous anticancer treatment has not recovered to ≤1, except for hair loss
12. A history of severe allergic reactions to humanized monoclonal antibodies or known allergies to any component of icp-022 or MIL62
13. Inability to swallow research drugs, or the presence of conditions that significantly affect gastrointestinal function, such as malabsorption syndrome, gastric or small bowel resection, symptomatic inflammatory bowel disease, or partial or complete intestinal obstruction
14. Hepatitis b surface antigen (HBsAg) and/or hepatitis b core antibody (HBcAb) are positive and Hepatitis B Virus(HBV) DNA exceeds the normal range; Hepatitis b surface antigen (HBsAg) and/or hepatitis b core antibody (HBcAb) positive do not agree to regular DNA testing, or do not receive antiviral preventive treatment; Hepatitis c virus (HCV) antibody positive and HCV RNA positive patients; Human immunodeficiency virus (HIV) serum response was positive;
15. Pregnant and lactating women; For women of childbearing age who have not undergone sterilization surgery: do not agree to use appropriate methods of contraception, such as oral contraceptives, intrauterine devices, barrier contraception or spermicide, during treatment and for at least 12 months after the last administration of the drug under study;
16. For men not undergoing sterilization: do not agree to use the barrier method of contraception during the study period and for at least 12 months after the last administration of the study drug, and do not agree to request their spouse to use other methods of contraception, such as oral contraceptives, intrauterine devices, barrier methods of contraception or spermicide;
17. Other circumstances considered inappropriate for the study by the investigator.