Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents for CLL/SLL

NCT04215809 | Recruiting Phase 1 FDA Drug

• 1 other identifier: APG2575CU101
• Study Type: interventional
• Target: 144
• Locations: 2 countries
• Sites: 9

Brief Summary

Assess the safety and tolerability, identify dose-limiting toxicities (DLT) and determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of lisaftoclax.

Conditions

CLL/SLL

Outcome Measures

Primary Outcomes (2)

• Primary Toxicity Endpoint: dose limiting toxicity (DLT)

  DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0

  42 days

• Maximally tolerated dose (MTD)

  MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment

  42 days

Study Arms (4)

Lisaftoclax 400mg

EXPERIMENTAL

Lisaftoclax 400mg ramp up

Drug: Lisaftoclax

Lisaftoclax 600mg

EXPERIMENTAL

Lisaftoclax 600mg ramp up

Drug: Lisaftoclax

Lisaftoclax 800mg

EXPERIMENTAL

Lisaftoclax 800mg ramp up

Drug: Lisaftoclax

Lisaftoclax 1000mg

EXPERIMENTAL

Lisaftoclax 1,000mg ramp up

Drug: Lisaftoclax

Interventions

Lisaftoclax DRUG

Lisaftoclax investigation drug in ramp up dosing

Lisaftoclax 1000mg; Lisaftoclax 400mg; Lisaftoclax 600mg; Lisaftoclax 800mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Histologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) according to the 2018 international workshop (IW) CLL criteria who must have relapsed or be refractory to at least one prior therapy for CLL/SLL and require treatment by 2018 IWCLL criteria. In addition, lisaftoclax (600 mg) plus acalabrutinib combination cohort may include patients who are: (1) treatment-naïve, or (2) refractory to venetoclax.
• Eastern Cooperative Oncology Group (ECOG) ≤ 2.
• Patient must have objectively documented evidence of disease progression prior to study entry such as: escalating lymphocytes count with an increase \> 50% over a period of two months or doubling time in less than 6 months; enlarging adenopathy or splenomegaly; increasing cytopenias; clinical B symptoms -night sweats, fatigue, \> 1% weight loss in 6 months, fevers \> 100.50F for ≥ one month without infection.
• Adequate bone marrow function independent of growth factor:
• Absolute neutrophil count (ANC) ≥1.0× 109/L in patient without bone marrow involvement. This criterion does not apply to patients with bone marrow involvement by CLL/SLL.
• Platelets count ≥30 x 109/L (entry platelet count must be independent of transfusion within 7 days of first dose of lisaftoclax).
• Adequate renal and hepatic function as indicated by:
• Serum creatinine ≤1.5×upper limit of normal (ULN); if serum creatinine is \>1.5×ULN, creatinine clearance must be ≥ 50 mL/min, calculated using the Cockcroft and Gault formula(140-Age)x mas (kg)/(72x creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976).
• Total bilirubin ≤1.5 x ULN, except patients with known Gilbert's syndrome.
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2.5 x ULN, Alkaline phosphatase\<2.5×ULN.
• International normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT) ≤1.5×ULN unless the patient is receiving anticoagulant therapy as long as PT or APTT is within therapeutic range of intended use of anticoagulants.
• Females of childbearing potential (i.e., not postmenopausal for at least 2 years or surgically sterile) must have negative results for pregnancy test performed:
• At screening on a serum sample obtained within 14 days prior to the first lisaftoclax administration;
• Prior to dosing on a urine sample obtained on the first day of lisaftoclax administration, if it has been \>7 days since obtaining the serum pregnancy test results.

You may not qualify if:

• Patient has undergone allogeneic stem cell transplant \< 90 days.
• Patient has active graft-versus-host disease or require immunosuppressive therapy.
• Patient has undergone CAR-T cell therapy \< 30 days.
• Richter's Syndrome (patients with previously treated Richter's syndrome will be permitted if they are in remission).
• Prior anti-BCL-2 treatment (except patients who discontinued treatment for reasons other than disease progression and patients in the lisaftoclax plus acalabrutinib cohort).
• For the acalabrutinib and lisaftoclax combination cohort: (1) Patients who discontinued due to acalabrutinib toxicity (Note: Patients who received a BTK inhibitor therapy may participate whether, or not, they progressed following BTK inhibitor treatment). (2) Patients who require treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, etc.) at study entry. (Patients receiving proton pump inhibitors who switch to H2 receptor antagonists or antacids are eligible for enrollment to this study arm.) (3) Patients who require or are receiving anticoagulation therapy with warfarin or equivalent vitamin K antagonists within 7 days of first dose of the study drug(s).
• Active pathogen infections including human immunodeficiency virus syndrome (HIV) infection.
• Has known central nervous system (CNS) involvement.
• Prior malignancy that required treatment and has shown recurrence within 2 years of screening (except for non-melanoma skin cancer or adequately treated carcinoma in situ of cervix or breast). Cancer treated within 2 years with curative intent and without recurrence as well as prostate cancer on active surveillance are allowed.
• Concurrent treatment with any other investigational agent, received biologics (≤28 days), or small molecule targeted therapies (≤5 half-life) or other anti-cancer therapies (including chemotherapy) ≤14 days of first dose of lisaftoclax.
• Patient is pregnant or breast feeding.
• Has received the following within 7 days prior to the first dose of lisaftoclax:
• Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for anti-neoplastic intent
• CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin
• Potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Novant Health

Charlotte, North Carolina, 28204, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Swedish Health

Seattle, Washington, 98122, United States

RECRUITING

Princess Alexandria Hospital

Brisbane, Queensland, QLD 4102, Australia

RECRUITING

Frankston Private Hospital

Melbourne, Victoria, 3199, Australia

RECRUITING

Related Publications (1)

• Davids MS, Chanan-Khan A, Ailawadhi S, Ivanov V, Usenko G, Nogaieva L, Kryachock I, Muzhychuk I, Perekhrestenko T, Kyselova O, Myasnikov A, Lukavetskyy L, Uspenskaya O, Marlton P, Proydakov A, Borisenkova E, Winter A, Siddiqi T, Lysa T, Bakirov B, Gabrail N, Ganju V, Konstantinova T, Samoilova O, Karpenko O, Osipov I, Mudenda B, Fu T, Chen Z, Liang Z, Mekala DJ, Li M, Glass L, Ahmad M, De A, Shah V, Wang H, Winkler RE, Yang D, Zhai Y. Safety, tolerability, and pharmacokinetics of lisaftoclax (APG-2575)-based therapy in patients with chronic lymphocytic leukemia: Phase 1b/2 study. Med. 2025 Dec 12;6(12):100885. doi: 10.1016/j.medj.2025.100885. Epub 2025 Oct 17.

  PMID: 41109219 DERIVED

MeSH Terms

Interventions

Lisaftoclax

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Central Study Contacts

Laura Glass

CONTACT

301-520-5964; Laura.Glass@ascentage.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The dose escalation study of APG-2575 as monotherapy will use the standard 3+3 design. APG-2575 will be taken orally, once daily starting with a ramp-up treatment and will receive the full dose starting on Day 1 of 28-Day-Cycle 1. The starting target dose of APG-2575 is 200 mg (using ramp-up) and will be increased in subsequent cohorts to 400 mg, 600 mg, 800 mg and 1200 mg accordingly.

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 2, 2020
• Study Start: March 2, 2020
• Primary Completion: October 31, 2025
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

US (7); AU (2)