Efficacy and Safety of Lisaftoclax (APG-2575) Monotherapy in Patients With Indolent Lymphoma

NCT07459608 | Not Yet Recruiting Phase 2

• 1 other identifier: Lisa-2025-777
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Indolent Lymphoma; WM; MZL; CLL / SLL

Outcome Measures

Primary Outcomes (1)

• safety and tolerance

  events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

  From the first dose to within 30 days after the last dose.

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to 24 months

• Complete Response Rate (CR)

  Up to 24 months

• Minimal Residual Disease (MRD) Negativity Rate

  Up to 24 months

• Progression-Free Survival (PFS)

  Up to 24 months

• Duration of Response (DOR)

  Up to 24 months

Study Arms (1)

Lisaftoclax Monotherapy

EXPERIMENTAL

Patients with histologically confirmed indolent B-cell lymphomas (CLL, WM, or 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 therapy, will receive lisaftoclax monotherapy. Lisaftoclax will be administered orally once daily with a dose ramp-up schedule to a target dose of 600 mg. Treatment will be given in 28-day cycles and continued until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.

Drug: Lisaftoclax

Interventions

Lisaftoclax DRUG

Continuous Monotherapy

Also known as: APG2575

Lisaftoclax Monotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at the time of signing the informed consent form (ICF).
• Histologically confirmed diagnosis of an indolent lymphoma (CLL/WM/MZL), meeting one of the following conditions:
• Cohort A: Previously untreated and ineligible for Bruton's Tyrosine Kinase inhibitor (BTKi) therapy due to severe comorbidities (e.g., uncontrolled hypertension, cardiac disease, or active infection, etc.).
• Cohort B: Received only one prior line of BTKi as first-line treatment, did not achieve a partial response (PR), and discontinued BTKi due to intolerable treatment-related adverse events (e.g., atrial fibrillation, hemorrhage, infection, rash, etc.).
• Adequate bone marrow function, defined as:
• Hemoglobin (Hb) ≥ 70 g/L (without transfusion support within 7 days prior to the first dose of study drug).
• Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L (independent of growth factor support within 7 days prior to the first dose of study drug).
• Platelet count ≥ 50 × 10⁹/L (without transfusion support within 7 days prior to the first dose of the study drug. If the patient has documented bone marrow involvement, a platelet count ≥ 30 × 10⁹/L is acceptable, provided the investigator ensures adequate supportive care).
• Adequate hepatic and renal function, defined as:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN).
• Creatinine clearance (Ccr) ≥ 40 ml/min (estimated by the Cockcroft-Gault formula).
• Total bilirubin \< 1.5 × ULN.
• Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal (LLN, 50%).
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 3.
• Life expectancy ≥ 3 months.

You may not qualify if:

• Prior treatment with any B-cell lymphoma 2 (BCL-2) inhibitor.
• Patients with active infection (including active hepatitis B virus \[HBV\] or hepatitis C virus \[HCV\] infection, or human immunodeficiency virus \[HIV\] positivity) or any other serious uncontrolled medical condition (Patients who are hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody (HBcAb) seropositive are eligible if their HBV DNA is below the lower limit of detection/quantification and they are willing to undergo monthly HBV reactivation monitoring. Patients who are HCV antibody positive are eligible if their HCV RNA is below the lower limit of detection/quantification).
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 12 months prior to the first dose of the study drug.
• Administration of any live vaccine within 28 days prior to the first dose of the study drug.
• Women of childbearing potential (WOCBP) or men with partners of childbearing potential who are unwilling to use highly effective contraception; pregnant or breastfeeding women.
• Inability to swallow tablets, or presence of malabsorption syndrome, any disease significantly affecting gastrointestinal function, gastrectomy/small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, or partial/complete bowel obstruction.
• Known hypersensitivity to the active pharmaceutical ingredient, excipients of the study drug, or its analogs.
• Requirement for concomitant treatment with strong inhibitors or inducers of cytochrome P450 (CYP) 3A.
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's judgment, could compromise the patient's safety or pose an undue risk for study participation.

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Henan cancer hospital

Zhengzhou, Henan, China

Location

MeSH Terms

Interventions

Lisaftoclax

Study Officials

• keshu Zhou, M.D

  Henan Cancer Hospital

  STUDY CHAIR

Central Study Contacts

Keshu Zhou, M.D

CONTACT

13674902391; dr_zkshu23810@163.com

Study Design

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

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 10, 2026
• Study Start: March 10, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)