Orelabrutinib Combined With Zuberitamab in the Initial Treatment of MZL

NCT06985472 | Recruiting Phase 2 DMC

• 1 other identifier: B2024-548-01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-center, prospective cohort study. The main purpose of study is to evaluate the efficacy and safety of Orelabrutinib combined with Zuberitamab in the initial treatment of MZL Main efficacy indicators Complete response rate (CR) at the end of combination therapy.

Conditions

Initial MZL; Untreated MZL; BTKi; CD20

Keywords

Orelabrutinib combined with Zuberitamab in the initial treatment of MZL

Outcome Measures

Primary Outcomes (1)

• 1Y CRR

  Complete response rate (CR) at the end of combination therapy Efficacy evaluation was performed every 3 cycles (12 weeks) during the treatment period, every 3 months during the maintenance treatment period, and every 3-6 months during the observation and follow-up period, using Lugano 2014 efficacy evaluation criteria. MRD tests are performed every 6 cycles within 2 years of starting the drug.For the main efficacy indicators, complete response rate (CR) and 95%CI were calculated.

  2 years

Secondary Outcomes (4)

• uMRD

  2 years

• ORR

  2 years

• PFSR in 24m

  2 years

• OSR in 24m

  2 years

Study Arms (1)

Trial group

EXPERIMENTAL

Orelabrutinib combined with Zuberitamab for 6 cycles induction therapy, after that patients were treated with Orelabrutinib combined with Zuberitamab (administered every 2 cycles) for 6 cycles or had disease progression or toxicity intolerance.

Drug: ZO

Interventions

ZO DRUG

Orelabrutinib 150mg, po, gd, D1-D28, every 28 days, cycle 1-12; Zuberitamab: intravenously administered on day 1 of the cycle at a dose of 375mg/m2 every 28 days, once every cycle for cycles 1-6 and once every 2 cycles for cycles 7-12.

Trial group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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 :
• blood routine examination standards must meet:
• ANC\>1.0×109/L;
• PLT\>75×109/L (≥50×109/L for patients with confirmed bone marrow infiltration);
• Hb\>80g/dL;
• Biochemical examination should meet the following criteria :
• TBIL\<2×ULN;
• ALT and AST\<2.5XULN(for patients with liver invasion,ALT and AST\<5×ULN);
• 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.

You may not qualify if:

• Patients with central nervous system invasion;
• Previous or co-existing uncured malignancies, except cured skin basal cell MZL clinical trial protocol cancer, cervical carcinoma in situ and superficial bladder cancer;
• 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;
• 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;
• 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;
• The presence of known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophiliac, coagulation disorder, thrombocytopenia, hypersplenism, etc.);
• Had major surgery or severe traumatic injury, fracture or ulcer within 4 weeks of enrollment;
• Have significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
• Active infections that require antimicrobial treatment (such as antimicrobial drugs, antiviral drugs, excluding chronic hepatitis B anti-hepatitis B treatment, antifungal drug treatment);
• 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);
• Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
• Had participated in other anti-tumor drug clinical trials within 4 weeks before enrollment;
• 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;
• Pregnant or lactating women; A fertile patient who is unwilling or unable to take effective contraceptive measures;
• The investigator determines other circumstances that may affect the conduct of the clinical study and the determination of the study results.

Sponsors & Collaborators

• Li Zhiming: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 515800, China

NOT YET RECRUITING

Central Study Contacts

Zhiming Li, professor

CONTACT

8613719189172; lizhm@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: November 13, 2024
• First Posted: May 22, 2025
• Study Start: November 13, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 22, 2025

Record last verified: 2025-05

Locations

CN (2)