Combining Orelabrutinib and Zuberitamab for treating Marginal Zone Lymphoma

Orelabrutinib Combined With Zuberitamab in the Initial Treatment of MZL Single-arm, Multicenter Phase II Clinical Study

This study is testing if combining two medications, Orelabrutinib and Zuberitamab, can help people with untreated Marginal Zone Lymphoma feel better and have fewer side effects.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: Zuberitamab, Orelabrutinib
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT06985472 on ClinicalTrials.gov

What this trial studies

This multi-center, prospective cohort study aims to evaluate the efficacy and safety of Orelabrutinib combined with Zuberitamab in patients with untreated Marginal Zone Lymphoma (MZL). Participants will receive 6 cycles of the ZO regimen induction therapy, followed by the combination treatment for an additional 6 cycles or until disease progression or intolerable toxicity occurs. The primary efficacy indicator is the complete response rate at the end of the combination therapy. This study seeks to explore more effective and low-toxicity treatment options for MZL patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed CD20-positive Marginal Zone Lymphoma who have not received prior systemic treatment.

Not a fit: Patients with early-stage MZL who have not experienced recurrence or progression after local treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective and less toxic option for patients with Marginal Zone Lymphoma.

How similar studies have performed: Other studies have shown promising results with BTK inhibitors in MZL, indicating that this approach may be effective.

Eligibility criteria

Inclusion Criteria:

1\. Age 18 years or older; 2. ECOG performance status (PS) level 0\~2; 3. The expected survival is not less than 12 weeks; 4. CD20-positive marginal area lymphoma confirmed according to WHO2008 lymphoma classification standard, including splenic MZL, lymph node MZL and extranodal MZL subtypes; 5. MZL with stage III/IV disease and stage I/II disease recurrence or progression after local treatment can also be included, and patients who have received BTKi inhibitor therapy for more than 6 months can also be included; 6. Enhanced computerized tomography/magnetic resonance imaging (CT/MRI) to detect measurable lesions; 7. Indications for MZL treatment that meet NCCN guidelines and have not received systematic treatment for MZL in the past (anti-infective treatment such as anti-HP and HCV is not systemic treatment); 8. The main organ function is normal and meet the following criteria :

1. blood routine examination standards must meet:

   1. ANC\>1.0×109/L;
   2. PLT\>75×109/L (≥50×109/L for patients with confirmed bone marrow infiltration);
   3. Hb\>80g/dL;
2. Biochemical examination should meet the following criteria :

   1. TBIL\<2×ULN;
   2. ALT and AST\<2.5XULN(for patients with liver invasion,ALT and AST\<5×ULN);
   3. Endogenous creatinine clearance ≥40ml/min (Cockcroft-Gault formula). 9. Women of childbearing age must have been using reliable contraception or had a pregnancy test (serum or urine) within 7 days of enrol with a negative result and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last dose of the test drug. For men, consent to use appropriate methods of contraception or surgical sterilization during the trial period and 8 weeks after the last dose of the trial drug; 10. The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

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      Exclusion Criteria:
      1. Patients with central nervous system invasion;
      2. Previous or co-existing uncured malignancies, except cured skin basal cell MZL clinical trial protocol cancer, cervical carcinoma in situ and superficial bladder cancer;
      3. Patients with the following cardiovascular diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval 2450 ms for men and 2470 ms for women); According to NYHA standards, patients with grade III to V cardiac insufficiency or left ventricular ejection fraction (LVEF) \<50% indicated by cardiac color ultrasound;
      4. Abnormal coagulation function (INR\>1.5 or prothrombin time (PT) \>ULN+4 seconds or APTT \>1.5 ULN), have a tendency to hemorrhage or are receiving thrombolytic or anticoagulant therapy;
      5. Arteriovenous thrombosis events occurring in the 12 months prior to enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
      6. The presence of known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophiliac, coagulation disorder, thrombocytopenia, hypersplenism, etc.);
      7. Had major surgery or severe traumatic injury, fracture or ulcer within 4 weeks of enrollment;
      8. Have significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
      9. Active infections that require antimicrobial treatment (such as antimicrobial drugs, antiviral drugs, excluding chronic hepatitis B anti-hepatitis B treatment, antifungal drug treatment);
      10. Active hepatitis B (HBV DNA\>2000IU/mL or 104 copy numbers /mL) or hepatitis C (hepatitis C antibody positive with HCVRNA higher than the lower detection limit of analytical methods);
      11. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
      12. Had participated in other anti-tumor drug clinical trials within 4 weeks before enrollment;
      13. Patients who had received potent CYP3A4 inhibitors within 7 days before enrollment, or had received potent CYP3A4 inducers within 12MZL clinical trial regimen days before enrollment;
      14. Pregnant or lactating women; A fertile patient who is unwilling or unable to take effective contraceptive measures;
      15. The investigator determines other circumstances that may affect the conduct of the clinical study and the determination of the study results.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Zhiming Li, professor

Conditions Initial MZL; Untreated MZL; BTKi; CD20; Orelabrutinib combined with Zuberitamab in the initial treatment of MZL