Lisatoclax Plus R-CHOP or Pola-R-CHP in Untreated DLBCL: A Phase Ib/II Study

A Phase Ib/II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Lisatoclax in Combination With R-CHOP or Pola-R-CHP in Patients With Previously Untreated DLBCL

This is a prospective, multicenter, open-label Phase Ib/II clinical study designed to evaluate the safety, tolerability, preliminary efficacy, and pharmacokinetics of lisatoclax in combination with R-CHOP or Pola-R-CHP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

Study Overview

• Status: Not yet recruiting
• Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
• Intervention / Treatment: Drug: R-CHOP; Drug: POLA-R-CHP; Drug: Lisaftoclax

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qingqing Cai, MD. PhD.; Phone Number: 02087342823; Email: caiqq@sysucc.org.cn
• Study Contact Backup: Name: Yi Xia, MD. PhD.; Phone Number: 02087342823; Email: xiayi@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
      • Contact: Qingqing Cai, M.D. Ph.D; Phone Number: 0086-20-87342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Voluntarily participate in the clinical study; fully understand and be informed about the study and sign the Informed Consent Form (ICF); willing to comply with and capable of completing all trial procedures.
• 2. Diagnosed with DLBCL according to 2022 revised WHO lymphoma classification standards based on pathological diagnosis by the research center. For the dose-expansion phase, BCL-2 positivity (≥50% by IHC) is required.
• 3. Age 18-70 years.
• 4. No prior systemic anti-lymphoma therapy.
• 5. Adequate organ and bone marrow function.
• 6. At least one measurable or evaluable disease site according to the Lugano 2014 lymphoma efficacy evaluation criteria.
• 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion Criteria:

• 1. Lymphoma involvement in the central nervous system or meninges.
• 2. Active infections.
• 3. Uncontrolled clinical cardiac symptoms or diseases.
• 4. Currently using (or unable to stop at least one week prior to the first dose) a known CYP3A strong inducer or strong inhibitor.
• 5. Pregnant and lactating women, and subjects of childbearing age who do not want to use contraception.
• 6. History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).
• 7. Patients with mental disorders or those unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lisatoclax Combined with R-CHOP or Pola-R-CHP; In Cohort 1, patients will receive standard-dose R-CHOP in combination with an initial dose of 400 mg of lisaftoclax. Each treatment cycle is 21 days. The lisaftoclax will be combined with R-CHOP at the RP2D dose level for an extension study. In Cohort 2, patients will receive standard-dose Pola-R-CHP in combination with an initial dose of 400 mg of lisaftoclax. Each treatment cycle is 21 days. The lisaftoclax will be combined with Pola-R-CHP at the RP2D dose level for an extension study.

Drug: R-CHOP; Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone; Drug: POLA-R-CHP; Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone; Drug: Lisaftoclax; Lisaftoclax (400 mg or 600 mg) is added from the second cycle of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT) for Phase 1b	To identify the DLT	The first cycle (each cycle is 21 days) after lisaftoclax administration.
Complete response rate (CRR) for Phase 2	The proportion of patients who achieve complete response (CR)	Up to 8 cycles (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The proportion of patients who achieve complete response (CR) or partial response (PR)	Up to 8 cycles (each cycle is 21 days)
Duration of Response (DOR)	To investigate the preliminary anti-tumor efficacy	Up to 5 years
Progression-free survival (PFS)	To investigate the preliminary anti-tumor efficacy	Up to 5 years
Overall survival (OS)	To investigate the preliminary anti-tumor efficacy	Up to 5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2031

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: February 7, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; R-CHOP protocol; Lisaftoclax
• Other Study ID Numbers: B2025-809

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No