Clinical Research Directory

Pirtobrutinib+Sonrotoclax（PS) Regimen in the Treatment of B-Cell Lymphoma

This prospective, open-label, Phase II clinical trial evaluates the efficacy and safety of pirtobrutinib combined with sotoclax across three distinct B-cell lymphoma cohorts: histologically transformed diffuse large B-cell lymphoma (DLBCL), relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and relapsed/refractory marginal zone lymphoma (MZL). Dosing regimen ：pirtobrutinib 200 mg orally once daily plus sotoclax with a 4-week dose escalation schedule (1, 2, 5, 10, 20, 40, 80, 160 mg/day, then 320 mg/day on days 1-28, starting Cycle 2) administered orally. Cohorts 1 and 2 additionally incorporate obinutuzumab 1000 mg intravenously on Cycle 1 days 1, 8, and 15, followed by days 1 of Cycles 2 through 6, with a maximum of six cycles. Each treatment cycle spans 28 days. For Cohort 1 (RT DLBCL), the primary objective centers on early response assessment following three cycles of the PSO regimen (pirtobrutinib-sotoclax-obinutuzumab), with PET/CT evaluation serving as the critical decision point. Patients demonstrating progressive disease or stable disease discontinue study treatment, while those achieving complete or partial response may proceed to investigator-selected bridging therapies including bispecific antibodies, CAR-T cell therapy, or hematopoietic stem cell transplantation, or alternatively continue PSO combination therapy. Obinutuzumab is capped at six cycles, whereas pirtobrutinib and sotoclax may continue for up to 25 cycles. Comprehensive biomarker strategies include ctDNA analysis from peripheral blood at baseline and after Cycle 1 (following full-dose sotoclax exposure), with serial assessments at Cycles 3, 7, 14, and every six cycles during Year 2 for patients continuing PSO beyond Cycle 3. Patients with measurable baseline tumor cells in peripheral blood or bone marrow undergo flow cytometry-based MRD detection at 10-⁴ sensitivity at corresponding timepoints. T-cell subset and functional analyses are performed at baseline, Cycle 3, and every three cycles thereafter to characterize immune dynamics during treatment. Cohort 2 (relapsed/refractory CLL/SLL) follows a continuous treatment paradigm without an early stopping rule, with efficacy assessment after fourteen cycles. Patients achieving complete remission with MRD negativity at 10-⁴ may elect treatment discontinuation. Sotoclax is administered for a maximum of twenty-four cycles, with pirtobrutinib maintenance for patients failing to achieve MRD-negative complete remission. The biomarker program incorporates both flow cytometry MRD at 10-⁴ and next-generation sequencing MRD at 10-⁶ sensitivity, providing unprecedented depth of residual disease characterization. Sampling occurs at baseline, Cycle 1, Cycle 3, Cycle 7, Cycle 14, and every six cycles in Year 2. Cohort 3 (relapsed/refractory MZL) mirrors the CLL/SLL treatment structure but omits obinutuzumab, testing the doublet of pirtobrutinib plus sotoclax. The fourteen-cycle efficacy assessment and MRD-guided stopping rule apply identically, with sotoclax limited to twenty-four cycles and pirtobrutinib maintenance for non-responders. ctDNA surveillance occurs at baseline, Cycle 3, Cycle 7, Cycle 14, and every six cycles in Year 2, complemented by serial T-cell immunophenotyping.

ROCKET-CLL Global Phase 3 Study: Rocbrutinib vs Pirtobrutinib in cBTKi-Pretreated R/R CLL/SLL

This is a Phase 3, randomized, open-label, multicenter study comparing rocbrutinib (LP-168) versus pirtobrutinib in adult participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent Bruton's tyrosine kinase inhibitor (cBTKi). Approximately 306 participants will be randomized 1:1 to receive rocbrutinib 200 mg orally once daily or pirtobrutinib 200 mg orally once daily, administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Randomization will be stratified by presence of del(17p)/TP53 mutation (yes/no), reason for discontinuation of prior cBTKi therapy (toxicity vs disease progression), prior exposure to a BCL2 inhibitor (yes/no), and region (United States/China/rest of world). The primary endpoint is progression-free survival (PFS) assessed by an independent review committee (IRC) using iwCLL 2018 criteria for CLL and Lugano 2014 criteria for SLL. Key secondary objectives include overall survival, overall response rate, time-to-event outcomes, and safety/tolerability; exploratory objectives include health-related quality of life and biomarker assessments.

A Study of Lonitoclax (ZE50-0134) in Relapsed or Refractory B-cell Malignancies

This Phase 1, open-label, multicenter study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of lonitoclax (ZE50-0134) in adults with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and select low-grade B-cell lymphomas. The study has two sequential parts. Part 1 uses dose escalation to determine the biologically effective dose and/or maximum tolerated dose of lonitoclax. Participants receive a 3-day step-up regimen followed by continuous once-daily or twice-daily oral dosing in 28-day cycles. Part 2 is a randomized dose-expansion comparison of two selected lonitoclax dose levels in venetoclax-naive participants with relapsed or refractory CLL/SLL. Treatment may continue for up to 12 cycles and, for participants deriving clinical benefit, for up to 24 cycles with approval from the Medical Monitor.

Efficacy and Safety of Lisaftoclax (APG-2575) Monotherapy in Patients With Mature B-cell Lymphoma

This is a multicenter, prospective, single-arm phase II study designed to evaluate the safety and efficacy of lisaftoclax (APG-2575), an oral selective BCL-2 inhibitor, in patients with indolent B-cell lymphomas. The study will enroll adult patients with chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM), or marginal zone lymphoma (MZL) who are either treatment-naïve but considered ineligible for Bruton tyrosine kinase (BTK) inhibitor therapy due to significant comorbidities, or who are intolerant to prior BTK inhibitor treatment. Eligible patients will receive oral lisaftoclax once daily with a dose ramp-up to a target dose of 600 mg in 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or completion of the planned treatment period. The primary objective is to evaluate the safety and tolerability of lisaftoclax monotherapy, while secondary objectives include assessment of antitumor activity, including overall response rate (ORR), complete response (CR) rate, minimal residual disease (MRD) negativity, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Quality of life will also be assessed using the EORTC QLQ-C30 questionnaire.

Zanubrutinib Induction Followed by Delayed Fixed-Duration Combination With Sonrotoclax for CLL/SLL：Stop Trial 2.0

The goal of this clinical trial is to learn if zanubrutinib induction followed by delayed fixed-duration combination with sonrotoclax works to treat previously untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). It will also learn about the safety of this combination regimen. The main questions it aims to answer are:Does this combination therapy achieve undetectable minimal residual disease (uMRD) in participants?What medical problems (adverse events) do participants have when taking zanubrutinib and sonrotoclax?Researchers will conduct a single-arm study to systematically evaluate the MRD clearance, efficacy, safety, and immune-related functions of this specific treatment sequence.Participants will:Low-risk group (without 17p deletion/TP53 mutation): Take zanubrutinib monotherapy for 12 cycles, followed by combination zanubrutinib + sonrotoclax for 12 cycles, then discontinue treatment for observation.High-risk group (with 17p deletion/TP53 mutation): Follow the same initial regimen (12 cycles monotherapy + 12 cycles combination), followed by zanubrutinib monotherapy maintenance until disease progression.Visit the clinic periodically for MRD assessment (via flow cytometry), efficacy evaluation (CT/PET-CT, lab tests), and safety checks (physical exam, blood tests, ECG).Undergo immune function evaluation via peripheral blood samples to assess changes in T-cell counts and subsets.