Orelabrutinib Combined With Obinutuzumab and Short-Course Venetoclax in Patients With Treatment-Naïve Mantle Cell Lymphoma (MCL)

Prior treatment

• Received prior treatment for lymphoma within 2 weeks before study enrollment;
• Diagnosis of or receiving treatment for another malignancy other than lymphoma, except for the following:
  • ①Malignancy that has been treated with curative intent and with no known active disease for ≥ 5 years prior to enrollment;
  • ②Adequately treated basal cell carcinoma of the skin (excluding melanoma) with no evidence of disease;
  • ③Adequately treated carcinoma in situ of the cervix with no evidence of disease;
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment;
• Requirement for anticoagulation therapy with warfarin or equivalent vitamin K antagonists;
• Requirement for long-term treatment with strong cytochrome P450 3A (CYP3A) inhibitors;
• Receipt of live attenuated vaccine within 4 weeks prior to enrollment.

Other illness

• Known active hepatitis C virus (HCV) infection; or other acquired or congenital immunodeficiency disorders, including but not limited to human immunodeficiency virus (HIV) infection;
• Known hypersensitivity to any study drug;

Lab values

• Any serious medical condition, including but not limited to:
  • Uncontrolled hypertension (defined as blood pressure that remains uncontrolled after at least 4 weeks of treatment with a reasonable and tolerable regimen of 3 or more antihypertensive agents \[including diuretics\] at adequate doses, or requiring 4 or more antihypertensive agents to achieve adequate control);
  • Uncontrolled congestive heart failure within 6 months prior to screening (New York Heart Association \[NYHA\] Class III \[moderate\] or Class IV \[severe\] cardiac disease);
  • Left ventricular ejection fraction (LVEF) \< 50%;
  • Symptomatic coronary artery disease (e.g., chest tightness, chest pain, palpitations, fatigue) or coronary artery disease requiring medical therapy; ⑤Severe bradycardia (heart rate \< 40 beats per minute \[bpm\]) with hypotension, dizziness, or syncope; patients with a history of arrhythmia should undergo cardiac evaluation;
  • Known active bacterial, viral, fungal, or other infection (excluding fungal infection of the nail bed), or major infection within 2 weeks prior to the first dose of study drug;
  • Moderate to severe hepatic impairment (Child-Pugh Class B or C); ⑧Active bleeding within 2 months prior to screening, or clear evidence of bleeding diathesis as judged by the investigator; ⑨Current pulmonary disease that impairs lung function, such as pulmonary fibrosis or drug-related pneumonitis, which is deemed intolerable by the investigator; ⑩Any psychiatric or cognitive disorder that may limit the patient's ability to understand, execute, or comply with the informed consent and study requirements;

Other

• All patients with central nervous system (CNS) involvement by lymphoma;
• Pregnant or breastfeeding women;

• Voluntarily participate and sign the informed consent form;
• Age ≥ 18 years, male or female;
• Life expectancy ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Patients with ECOG 3 may be enrolled only if the decline in performance status is attributed to the underlying disease and the investigator determines that they may benefit from the treatment;
• Pathologically confirmed diagnosis of mantle cell lymphoma (MCL) and treatment-naïve;
• Presence of measurable and/or evaluable lymphoma lesions;
• Adequate bone marrow reserve, defined as: absolute neutrophil count \> 1.0×10⁹/L or platelet count \> 75×10⁹/L, unless cytopenias are considered to be related to bone marrow involvement by lymphoma and deemed recoverable by the investigator;
• Hepatic function: AST (SGOT) and ALT (SGPT) ≤ 2.5 × upper limit of normal (ULN) (in the absence of liver involvement) or ≤ 5 × ULN (in the presence of liver involvement); total bilirubin (TBIL) ≤ ULN; serum creatinine (CRE) ≤ 1.5 × ULN;
• Creatinine clearance ≥ 30 mL/min, calculated using the Cockcroft-Gault formula;
• Able to comply with the study visit schedule and other protocol requirements;
• All patients of childbearing potential must agree to use effective contraceptive measures during the study and for 24 months after study treatment discontinuation. Female patients of childbearing potential must have a negative urine pregnancy test prior to the first dose of study treatment.