A Phase II Study of TT-01488 Tablets in Combination With Anti-CD20 Monoclonal Antibody Therapy in Patients With Mantle Cell Lymphoma

Prior treatment

• Participants whose treatment intent is tumor debulking prior to stem cell transplantation;
• Severe cardiovascular disease within 6 months prior to screening;
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug;
• History of bleeding diathesis (e.g., hemophilia, von Willebrand disease); requiring or currently receiving anticoagulation with warfarin or equivalent vitamin K antagonists;
• Requires strong CYP3A4 inhibitors or inducers. Strong CYP3A4 inhibitors within 1 week or strong CYP3A4 inducers within 3 weeks before first dose of study drug are prohibited;

Other illness

• Active central nervous system (CNS) involvement by lymphoma, leptomeningeal disease, or history of spinal cord compression;
• Any active major infection (e.g., bacterial, viral, or fungal), including CMV DNA PCR-positive participants;
• Serological evidence of active hepatitis B or hepatitis C infection;
• Known history of human immunodeficiency virus (HIV) infection;
• Malabsorption syndrome or significant gastrointestinal dysfunction (e.g., gastrectomy, small bowel resection, symptomatic inflammatory bowel disease, complete/incomplete intestinal obstruction).

Age

• Concurrent or prior malignancy, except adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancers with no disease progression for ≥2 years;

• Combination Cohort A: Part A (dose exploration): Age ≥18 years; no requirement for transplant ineligibility. Part B (efficacy exploration): Age ≥65 years, or 60 to \<65 years with ≥1 of the following criteria for autologous stem cell transplantation (auto-SCT) ineligibility:① left ventricular ejection fraction (LVEF) ≤45%;② creatinine clearance (CrCl) 30-\<70 mL/min;③ diffusing capacity of the lung for carbon monoxide (DLCO) ≤60% predicted;④ Eastern Cooperative Oncology Group performance status (ECOG PS) 2;⑤ cumulative illness rating scale (CIRS) total score \>6;⑥ other comorbidities precluding intensive induction chemotherapy and transplantation, as assessed by the investigator;
• Combination Cohorts B and C: Age ≥18 years;
• Histologically confirmed MCL, CD20-positive, with documented high Cyclin D1 expression by immunohistochemistry (IHC) and/or positive t(11;14) by cytogenetics;
• Ann Arbor clinical stage II-IV;
• Part A (Dose exploration): ≥1 prior line of therapy, relapsed/refractory disease, no prior BTK inhibitor, and ≤3 total prior lines.Part B (Efficacy exploration): No prior systemic therapy for MCL;
• At least one measurable lesion;
• ECOG performance status 0-2;
• Adequate organ function within 7 days before first dose;
• Women of childbearing potential: negative pregnancy test before treatment and effective contraception during the study and for 6 months after the last dose; male participants: effective contraception during the same period;
• Written informed consent obtained before study participation.