This is an open-label, multicenter, phase 2, non-randomized study aiming to evaluate the efficacy and safety of orelabrutinib combined with zebetuzumab and lenalidomide or bendamustine combined with rituximab in the treatment of newly diagnosed marginal zone lymphoma (MZL).
1. Age 18-75 years, gender not restricted;
2. Histopathologically confirmed CD20-positive marginal zone lymphoma includes MALT, SMZL, and NMZL; at least one measurable lesion;
3. Indication for treatment
3.1. Initial diagnosis II 2 or IIE or IV stage gastric MALT treatment indications. Including: ① Meeting the inclusion criteria for clinical trials; ② Presence of lymphoma-related clinical symptoms; ③ Gastrointestinal bleeding (bleeding condition controlled or assessed by the investigator for suitability of inclusion); ④ End-organ damage; ⑤ Large mass; ⑥ Persistent or rapid disease progression; ⑦ Patient's willingness;
1. Currently or previously diagnosed with other malignancies, unless radical treatment has been performed and there is evidence of no recurrence or metastasis within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, and localized squamous cell carcinoma of the skin;
2. Lymphoma involving the central nervous system or transforming to a higher grade;
3. Uncontrolled or significant cardiovascular diseases, including: a) Occurrence of New York Heart Association (NYHA) Class III-IV congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first administration of the investigational drug, or the presence of treatable arrhythmias at screening, with left ventricular ejection fraction (LVEF) <50%; b) Primary cardiomyopathies (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy); c) A clinically significant history of QTc interval prolongation, or QTc interval during the screening period >470ms for females and >450ms for males; d) Subjects with symptomatic or medication-requiring coronary heart disease; e) Suffering from uncontrolled hypertension (blood pressure remains uncontrolled after more than one month of using a reasonable and tolerable dosage of three or more antihypertensive drugs (including diuretics) based on lifestyle improvements, or blood pressure can only be effectively controlled by taking four or more antihypertensive drugs);
4. Active bleeding within 2 months prior to screening, or currently taking anticoagulants, or deemed by the investigator to have a clear bleeding tendency;
Parallel
Orelabrutinib
DrugInduction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Orelabrutinib (150 mg, d1-d28). Maintenance phase (a total of 24 cycles, each cycle lasting 28 days), Orelabrutinib (150 mg, d1-d28). Patients who achieve complete remission (CR) or partial remission (PR) after 6 cycles will decide whether to undergo maintenance therapy based on the investigator's choice.
Zebetuzumab
DrugInduction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Zebetuzumab (375 mg/m2, d1/C1-C6).
Lenalidomide
DrugInduction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Lenalidomide (20 mg, d1-d21).
Bendamustine + Rituximab
DrugTreatment period (a total of 6 cycles, each cycle lasting 28 days), Bendamustine (90 mg/m2, d1-2), Rituximab (375 mg/m2, d1/C1-6).
3-year PFS rate
PFS is defined as the first dose of treatment to the date of first documented progression or date of death from any cause, whichever occurs first. 3-year PFS rate will be estimated by Kaplan-Meier.
Overall response rate (ORR)
Overall response rate is the proportion of patients who achieve either a complete or partial response to treatment defined by the Lugano classification criteria for lymphoma response evaluation (2014 edition)/GELA (gastric MALT).
Rate of best overall response (BOR)
The rate of best overall response is the proportion of patients who achieve their best recorded response (complete or partial) to treatment at any time during the study.
Time to response (TTR)
Time to response is the duration from the start of treatment to the first documentation of a complete or partial response.
Progression-free survival (PFS) rate
PFS is defined as the time from the first dose of treatment until the date of first documented progression or date of death from any cause, whichever occurs first. For subjects without progression, relapse, or death at the time of analysis, EFS will be censored at the last assessment date.
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