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
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 122
- Locations
- 1
- Primary Endpoint
- Dose-limiting toxicity (DLT) for Phase 1b
Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: R-CHOP (Drug)
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.
Intervention: POLA-R-CHP (Drug)
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.
Intervention: Lisaftoclax (Drug)
Outcomes
Primary Outcomes
Dose-limiting toxicity (DLT) for Phase 1b
Time Frame: The first cycle (each cycle is 21 days) after lisaftoclax administration.
To identify the DLT
Complete response rate (CRR) for Phase 2
Time Frame: Up to 8 cycles (each cycle is 21 days)
The proportion of patients who achieve complete response (CR)
Secondary Outcomes
- Overall response rate (ORR)(Up to 8 cycles (each cycle is 21 days))
- Duration of Response (DOR)(Up to 5 years)
- Progression-free survival (PFS)(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
Investigators
Qingqing Cai
chief physician
Sun Yat-sen University