Treatment of relapsed/refractory diffuse large B-cell lymphoma with BEBT-908 and other drugs

A Multicenter, Open Phase Ib Study of the Safety and Efficacy of BEBT-908 Combined With Drugs in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This study is testing a new drug called BEBT-908 combined with other treatments to see if it can help people with relapsed or hard-to-treat diffuse large B-cell lymphoma feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: BeBetter Med Inc (Industry-sponsored)
• Drugs / interventions: CAR-T, chimeric antigen receptor, chemotherapy, immunotherapy, prednisone, Rituximab
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06164327 on ClinicalTrials.gov

What this trial studies

This multicenter Phase Ib clinical study evaluates the safety, efficacy, and pharmacokinetics of BEBT-908 when combined with Rituximab, Rituximab-Gemcitabine-Oxaliplatin, or Rituximab-Ifosfamide-Carboplatin-Etoposide in patients with relapsed or refractory diffuse large B-cell lymphoma. The study is structured into three cohorts based on the drug combinations, with the possibility of alternative cohorts if participants cannot receive the initial treatments. Participants will undergo a screening period, treatment period, and post-treatment follow-up, with tumor evaluations every six weeks during treatment. The study aims to determine the tolerability and effectiveness of these combinations in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with confirmed diffuse large B-cell lymphoma who have experienced relapse or refractory disease after at least one systemic therapy.

Not a fit: Patients who have not received prior systemic therapy or those with other types of lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory diffuse large B-cell lymphoma.

How similar studies have performed: Other studies have shown promise with similar drug combinations in treating diffuse large B-cell lymphoma, but this specific combination is novel.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing, China (Recruiting)

Study contacts

• Principal investigator: Yuankai Shi, Phd — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Kegang Jiang, Master

Conditions Relapsed/Refractory Diffuse Large B-Cell Lymphoma; BEBT-908; Drug combination; Safety; Efficacy