eligibility_summary
Eligibility: ≥18, R/R CLL/SLL or MCL (WHO/iwCLL), ≥2 prior systemic lines incl BTKi, measurable disease for R/R MCL, ECOG 0–1, life ≥6 mo, adequate heme/hepatic/renal/pulmonary/cardiac and coagulation, contraception, able to comply. Exclude: CNS involvement, Richter’s, allo-SCT, auto-SCT or CAR-T <3 mo, strong CYP3A/2C8 within 5 half-lives/plan to use, active IV infection, immunodeficiency/HIV, major CV, CNS disorders, unresolved ≥G2 AEs, substance abuse, GI malabsorption/surgery, can’t swallow.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I, recruiting. Interventions: ICP-248 (oral small‑molecule BCL‑2 inhibitor) as monotherapy or combined with anti‑CD20 antibodies: obinutuzumab (type II, glycoengineered anti‑CD20 monoclonal antibody) in CLL/SLL and rituximab (type I anti‑CD20 monoclonal antibody) in MCL. Mechanisms: ICP-248 blocks the anti‑apoptotic BCL‑2 protein, restoring mitochondrial (intrinsic) apoptosis in malignant B cells (via BAX/BAK activation). Obinutuzumab depletes CD20+ B cells through enhanced antibody‑dependent cellular cytotoxicity (ADCC) and direct cell death, rituximab depletes CD20+ B cells via complement‑dependent cytotoxicity (CDC) and ADCC. Targets: mature CD20+ B cells in CLL/SLL and MCL, pathways include BCL‑2–mediated apoptosis and CD20‑mediated immune clearance.