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

NCT07744750 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026CELH027-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CLL / SLL; MZL; Richter Transformation; DLBCL - Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) after 14 cycles of induction therapy

  Objective Response Rate (ORR) after 14 cycle induction therapy

  week 56，at the end of 14 cycle of PSO/PS regimen（each cycle is 28 days）

Secondary Outcomes (4)

• Complete Response Rate (CRR) after 14 cycles of induction therapy

  week 56，at the end of 14 cycle of PSO/PS regimen（each cycle is 28 days）

• Overall Survival (OS)

  up to 3 years

• Event-Free Survival (EFS)

  up to 3 years

• Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0

  up to 3 years

Study Arms (1)

PS+/-O for B cell lymphoma

EXPERIMENTAL

Cohort1：Pirtobrutinib, Sotoclax, and Obinutuzumab (PSO) Combination for RT DLBCL Cohort2： Pirtobrutinib, Sotoclax, and Obinutuzumab (PSO) Combination for R/R CLL/SLL Cohort3：Pirtobrutinib and Sotoclax Combination for R/R MZL

Drug: Pirtobrutinib, Sotoclax+/- Obinutuzumab (PSO) Combination for B cell lymphoma

Interventions

Pirtobrutinib, Sotoclax+/- Obinutuzumab (PSO) Combination for B cell lymphoma DRUG

Pirtobrutinib, Sotoclax+/- Obinutuzumab (PSO) Combination for B cell lymphoma

PS+/-O for B cell lymphoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1: Histologically transformed DLBCL
• Histopathologically confirmed histologically transformed DLBCL, including transformation from indolent lymphomas such as CLL, WM, FL, and MZL.
• Whole-body PET/CT performed within 28 days prior to study enrollment demonstrating at least one measurable lesion in two perpendicular dimensions (longest diameter \>15 mm for nodal lesions, or longest diameter \>10 mm for extranodal lesions).
• Except patients with Richter transformation, patients transformed from MZL, FL, WM, etc., must have received at least one line of systemic anti-lymphoma therapy either during the indolent phase or after transformation.
• Cohort 2: Relapsed/refractory CLL/SLL
• Histopathologically confirmed relapsed/refractory CLL/SLL.
• Disease relapse or refractoriness after at least one line of systemic anti-lymphoma therapy, which may include a BTK inhibitor.
• Cohort 3: Relapsed/refractory MZL
• Histopathologically confirmed relapsed/refractory MZL. 2.Received systemic therapy containing an anti-CD20 monoclonal antibody or a BTK inhibitor.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. 4.Age ≥ 18 years. 5.Adequate organ and bone marrow function defined as follows:
• Hematologic function (assessed within 7 days prior to Cycle 1 Day 1 \[C1D1\]): a. Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L. Patients with values below this threshold may be eligible if there is documented bone marrow involvement impairing hematopoiesis. b. Platelet count ≥ 50 × 10⁹/L without transfusion support. Patients with values below this threshold may be eligible if there is documented bone marrow infiltration impairing hematopoiesis. c. If transfusions are administered to treat thrombocytopenia or anemia, the patient must demonstrate a response to transfusion support.
• Coagulation function: Activated partial thromboplastin time (aPTT), prothrombin time (PT), or international normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN).
• Hepatic function: Serum total bilirubin (TBIL) ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
• Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 30 mL/min.
• Cardiac function: New York Heart Association (NYHA) functional class less than Class III; ejection fraction ≥ 50% on echocardiogram.

You may not qualify if:

• DLBCL with central nervous system or leptomeningeal involvement;
• Prior treatment with a non-covalent BTK inhibitor;
• Prior treatment with immune checkpoint inhibitors;
• Contraindication or hypersensitivity to any drug in the combination treatment regimen;
• Concurrent other malignancies requiring treatment or intervention;
• Major surgery within 4 weeks prior to treatment (excluding vascular access catheterization or biopsy);
• Any life-threatening disease, medical condition or organ dysfunction that, in the Investigator's opinion, may compromise patient safety or compliance with study procedures;
• Uncontrolled clinical cardiac signs or diseases, including: i. Heart failure of NYHA Class ≥ II ii. Unstable angina pectoris iii. Myocardial infarction within the past 12 months iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• Patients with active bleeding;
• Active and uncontrolled systemic bacterial, viral, fungal or parasitic infection (excluding fungal nail infection), or other clinically significant active disease process rendering the patient unsuitable for trial participation as judged by the Investigator.
• Patients with active chronic hepatitis B or active hepatitis C. Patients positive for Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb), or Hepatitis C virus (HCV) antibody at screening must undergo further Hepatitis B virus (HBV) DNA testing (≤2500 copies/mL or ≤500 IU/mL) to rule out active hepatitis B or active hepatitis C requiring treatment before enrollment. Nevertheless, eligible patients with positive HBsAg and/or HBcAb must receive anti-hepatitis B antiviral therapy.
• Patients infected with Human Immunodeficiency Virus (HIV) and/or patients with acquired immunodeficiency syndrome (AIDS);
• Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect absorption of the study drug;
• Pregnant or lactating women;
• Patients with psychiatric disorders or those unable to provide informed consent;

Sponsors & Collaborators

• Changzhou No.2 People's Hospital: lead

Study Sites (1)

Jiangsu Province Hospital The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

Location

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Interventions

pirtobrutinib

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Huayuan Zhu, PhD

CONTACT

+86 13813810650; huayuan.zhu@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 4, 2026
• Study Start (Estimated): August 30, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2029
• Last Updated: August 4, 2026

Record last verified: 2026-07

Locations

CN (1)