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 comprehensive understanding; 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 2016 World 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 measurable lesion injection; 5. Must have recurrent or refractory diffuse large B-cell lymphoma after at least 1 systemic 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: 1. Absolute neutrophil count (ANC) ≥1000/μL; 2. Hemoglobin (HGB) ≥8g/dL; 3. Platelet count (PLT) ≥100,000/μL; Liver function: 1. Serum total bilirubin ≤1.5×ULN (for patients with Gilbert syndrome, total bilirubin \<3.0×ULN and Direct bilirubin within normal range); 2. Serum creatinine \<1.5×ULN; 3. 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 the investigational drug, the following subjects should be excluded: 1. Men and women who have not had sperm or egg preservation in vitro before the trial and plan to have another child within 5 years unless subsequent studies confirm reproductive safety; 2. Pregnant or lactating women; 3. Primary central nervous system lymphoma or lymphoma invading the central nervous system; 4. Previous chronic lymphoma transformation (such as Richter syndrome, prelymphocytic leukemia, etc.); 5. There are other active malignant tumors requiring treatment that may interfere with the study; 6. Pre-trial treatment: 1. Received any persistent or intermittent PI3K inhibitor and HDAC inhibitor prior to enrollment or received other small-molecule targeted drug therapy within 2 weeks; 2. Received BEBT-908 (not allowed to be in all cohorts) or R-ICE (not allowed to be in cohorts with BEBT-908+R-ICE) or R-GemOx (not allowed to be in cohorts with BEBT-908+R-GemOx) prior to enrollment; 3. Autologous hematopoietic stem cell transplantation within 3 months before enrollment; 4. Received radiotherapy that affected the evaluation of the efficacy of the study or local supportive radiotherapy that affected the bone marrow function of the subjects within 3 months before enrollment; 5. Received myelosuppressive chemotherapy or biotherapy within 3 weeks prior to enrollment; 6. Used Chinese medicines and proprietary Chinese medicines with anti-tumor effects within 2 weeks before enrollment; 7. Undergone major surgery other than tumor biopsy within 4 weeks prior to enrollment, or the side effects of surgery had not stabilized; 8. Any hematopoietic colony-stimulating factor (e.g., granulocyte colony-stimulating factor G-CSF, granulocyte macrophage colony-stimulating factor GM-CSF) or thrombopoietin TPO were treated within 2 weeks prior to enrollment； 9. Received prednisone \>10mg daily (or another equivalent dose of glucocorticoid) within 7 days prior to enrollment; 10. Received chimeric antigen receptor T cell immunotherapy (CAR-T therapy) within 3 months before enrollment; 7. Persistent grade 2 or higher \[Common Terminology Criteria for Adverse Events V5.0 standard (CTCAE V5.0 standard)\] toxicity after previous treatment (chemotherapy or biotherapy), not stable at enrollment (except alopecia); 8. Active clinical severe infection of grade 2 or above (CTCAE V5.0 standard); 9. Complicated diseases: 1. diabetes mellitus with poor glycemic control (random glycemic value ≥11.1mmol/L after hypoglycemic treatment, or glycosylated hemoglobin（HbA1c）≥ 8.5%); 2. severe lung disease (CTCAE V5.0 grade III-IV); 3. Serious heart disease; 4. have significant kidney or liver dysfunction; 5. Poorly controlled active diseases such as hepatitis B or C; 6. Known human immunodeficiency virus (HIV) positive; 7. A history of mental illness, family history of mental illness, or mood disorder, as judged by the investigator or psychologist, and the researcher judged that they were not suitable for inclusion; 8. Combination of anticoagulation and antiplatelet therapy is required during the study period; 9. uncontrolled hypertension (systolic blood pressure ≥180mmHg and/or diastolic blood pressure ≥110mmHg); 10. Serious physical disease combined with the risk of major bleeding or a history of major bleeding; 10. Combined with use of drugs that cause QT interval prolongation or torsional ventricular tachycardia; 11. Receiving cytochrome P450 (CYP) 3A4 isozyme suppressant or strongly induced drug therapy during the first 4 weeks of enrollment； 12. Participated in other clinical trials and used investigational drugs within 4 weeks before enrollment; 13. Any condition that the investigator determines to be unstable or likely to compromise the subject's safety and compliance with the study; 14. Subjects deemed unsuitable for treatment with this protocol by the investigator.