Study of BEBT-908 Combined With Drugs in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

1. The subject is willing to sign the informed consent form (ICF) after comprehensiveunderstanding;
2. Age ≥18 years and ≤75 years, both male and female;
3. The pathology was confirmed as diffuse large B-cell lymphoma according to the 2016World Health Organization classification definition;
4. Evaluation by Positron Emission Computed Tomography (PET-CT) or Computed Tomography (CT) or Magnetic resonance imaging (MRI) using Lugano 2014 standard, with measurablelesion injection;
5. Must have recurrent or refractory diffuse large B-cell lymphoma after at least 1systemic therapy, and at least 1 systemic therapy included CD20 antibody;
6. Eastern Cooperative Oncology Group (ECOG) scores 0-2 points;
7. Life expectancy >12 weeks;
8. The level of organ function must meet the following requirements: Peripheral blood:
9. Absolute neutrophil count (ANC) ≥1000/μL;
10. Hemoglobin (HGB) ≥8g/dL;
11. Platelet count (PLT) ≥100,000/μL; Liver function:
12. Serum total bilirubin ≤1.5×ULN (for patients with Gilbert syndrome, total bilirubin <3.0×ULN and Direct bilirubin within normal range);
13. Serum creatinine <1.5×ULN;
14. ALT, AST or ALP≤2.5×ULN (≤5×ULN when liver involvement occurs).

Exclusion Criteria:

1. Known severe allergy to the investigational drug or any of its excipients;
2. Due to the possibility of genotoxicity, mutagenicity and teratogenicity of theinvestigational drug, the following subjects should be excluded:
3. Men and women who have not had sperm or egg preservation in vitro before thetrial and plan to have another child within 5 years unless subsequent studiesconfirm reproductive safety;
4. Pregnant or lactating women;
5. Primary central nervous system lymphoma or lymphoma invading the central nervoussystem;
6. Previous chronic lymphoma transformation (such as Richter syndrome, prelymphocyticleukemia, etc.);
7. There are other active malignant tumors requiring treatment that may interfere withthe study;
8. Pre-trial treatment:
9. Received any persistent or intermittent PI3K inhibitor and HDAC inhibitor priorto enrollment or received other small-molecule targeted drug therapy within 2weeks;
10. Received BEBT-908 (not allowed to be in all cohorts) or R-ICE (not allowed to bein cohorts with BEBT-908+R-ICE) or R-GemOx (not allowed to be in cohorts withBEBT-908+R-GemOx) prior to enrollment;
11. Autologous hematopoietic stem cell transplantation within 3 months beforeenrollment;
12. Received radiotherapy that affected the evaluation of the efficacy of the studyor local supportive radiotherapy that affected the bone marrow function of thesubjects within 3 months before enrollment;
13. Received myelosuppressive chemotherapy or biotherapy within 3 weeks prior toenrollment;
14. Used Chinese medicines and proprietary Chinese medicines with anti-tumor effectswithin 2 weeks before enrollment;
15. Undergone major surgery other than tumor biopsy within 4 weeks prior toenrollment, or the side effects of surgery had not stabilized;
16. Any hematopoietic colony-stimulating factor (e.g., granulocyte colony-stimulatingfactor G-CSF, granulocyte macrophage colony-stimulating factor GM-CSF) orthrombopoietin TPO were treated within 2 weeks prior to enrollment；
17. Received prednisone >10mg daily (or another equivalent dose of glucocorticoid)within 7 days prior to enrollment;
18. Received chimeric antigen receptor T cell immunotherapy (CAR-T therapy) within 3months before enrollment;
19. Persistent grade 2 or higher [Common Terminology Criteria for Adverse Events V5.0standard (CTCAE V5.0 standard)] toxicity after previous treatment (chemotherapy orbiotherapy), not stable at enrollment (except alopecia);
20. Active clinical severe infection of grade 2 or above (CTCAE V5.0 standard);
21. Complicated diseases:
22. diabetes mellitus with poor glycemic control (random glycemic value ≥11.1mmol/Lafter hypoglycemic treatment, or glycosylated hemoglobin（HbA1c）≥ 8.5%);
23. severe lung disease (CTCAE V5.0 grade III-IV);
24. Serious heart disease;
25. have significant kidney or liver dysfunction;
26. Poorly controlled active diseases such as hepatitis B or C;
27. Known human immunodeficiency virus (HIV) positive;
28. A history of mental illness, family history of mental illness, or mood disorder,as judged by the investigator or psychologist, and the researcher judged thatthey were not suitable for inclusion;
29. Combination of anticoagulation and antiplatelet therapy is required during thestudy period;
30. uncontrolled hypertension (systolic blood pressure ≥180mmHg and/or diastolicblood pressure ≥110mmHg);
31. Serious physical disease combined with the risk of major bleeding or a history ofmajor bleeding;
32. Combined with use of drugs that cause QT interval prolongation or torsionalventricular tachycardia;
33. Receiving cytochrome P450 (CYP) 3A4 isozyme suppressant or strongly induced drugtherapy during the first 4 weeks of enrollment；
34. Participated in other clinical trials and used investigational drugs within 4 weeksbefore enrollment;
35. Any condition that the investigator determines to be unstable or likely to compromisethe subject's safety and compliance with the study;
36. Subjects deemed unsuitable for treatment with this protocol by the investigator.