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

Sun Yat-sen University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Diffuse Large B Cell Lymphoma (DLBCL)

Treatments: Drug: POLA-R-CHP; Drug: Lisaftoclax; Drug: R-CHOP

Study type: Interventional

Funder types: Other

Identifiers

NCT07398638

B2025-809

Details and patient eligibility

About

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).

Enrollment: 122 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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122 participants in 1 patient group

Lisatoclax Combined with R-CHOP or Pola-R-CHP

Experimental group

Description:

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.

Treatment:

Drug: R-CHOP

Drug: Lisaftoclax

Drug: POLA-R-CHP