APG-2575 Single Agent or in Combination With Ibrutinib or Rituximab in Patients With Waldenström Macroglobulinemia

NCT04260217 | Completed Phase 1 FDA Drug

• 1 other identifier: APG2575WU101
• Study Type: interventional
• Target: 46
• Locations: 3 countries
• Sites: 14

Brief Summary

Phase Ib/II study of safety, tolerability, efficacy and PK of APG-2575 as a single agent or in combination with other therapeutic agents including ibrutinib or rituximab.

Conditions

Waldenstrom Macroglobulinemia

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 (3)

APG2575 400 mg

EXPERIMENTAL

APG2575 400mg ramp up arm

Drug: APG2575 400 mg; Drug: APG2575 600 mg; Drug: APG2575 800 mg

APG2575 600 mg

EXPERIMENTAL

APG2575 600 mg ramp up arm

Drug: APG2575 600 mg; Drug: APG2575 800 mg

APG2575 800 mg arm

EXPERIMENTAL

APG2575 800 mg arm ramp up

Drug: APG2575 800 mg

Interventions

APG2575 400 mg DRUG

APG2575 400 mg

APG2575 400 mg

APG2575 600 mg DRUG

APG2575 600 mg

APG2575 400 mg; APG2575 600 mg

APG2575 800 mg DRUG

APG2575 800 mg

APG2575 400 mg; APG2575 600 mg; APG2575 800 mg arm

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Local confirmed clinicopathological diagnosis of WM in accordance with the consensus panel of the Second International Workshop on WM (Owen 2003).
• WM patients with symptomatic and measurable disease (defined as presence of serum immunoglobulin M (IgM)\>0.5g/dL), requiring treatment as per mSMART guidelines (Kyle 2003): with B symptoms (fever, night sweats, fatigue, night sweats weight loss), progressive lymphadenopathy or splenomegaly, anemia (hemoglobin value of \<10 g/dL) or platelet count \<100\*109/L due to marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy due to WM, systemic amyloidosis related to WM, renal insufficiency related to WM, or symptomatic cryoglobulinemia may also be indications for therapy.
• For Arm A only: Have received at least one prior therapy for WM. Patient must have either failed (defined as progressing while on or within 6 months of treatment with ibrutinib treatment) or intolerant to ibrutinib.
• For Arm B only: Previously untreated WM.
• For Arm C only: Have received at least one prior therapy, relapsed or refractory WM.
• Adequate hematologic function defined as:
• ANC ≥1.0 x 109/L independent of growth factor support within 7 days of the first dose with study drug.
• Hemoglobin ≥9 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug.
• Platelet count ≥ 75 x 109/L without transfusion support within 7 days of the first dose of study drug.
• Adequate hepatic and renal function defined as:
• AST and ALT \< 2.5 x ULN (upper limit of normal)
• Glomerular filtration rate (GFR) \>30mL/min
• Bilirubin\< 1.5 x ULN
• PT/INR ≤1.5 x ULN and PTT (aPTT) ≤1.5 x ULN.
• ≥18 years of age.

You may not qualify if:

• For Arm A only: Patients who have never been treated with ibrutinib.
• For Arm B only: Patients who have previously received any treatment for WM.
• For Arm C only:
• Patients who have previously been treated with ibrutinib or other BTK inhibitor.
• Disease that is refractory to the last prior rituximab based-therapy defined as either Relapse after the last rituximab-based therapy (\<12 months since last dose of rituximab), OR Failure to achieve at least a MR after the last rituximab-based therapy.
• Rituximab treatment within the last 12 months before the first dose of study drug.
• Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab.
• Patients with central nervous system involvement (Bing-Neel syndrome), active infection (including active hepatitis B or C virus infection, known human immunodeficiency virus (HIV) positive) or any other serious (unresolved) medical condition.
• Plasmapheresis \<35 days prior to the initiation of study drug. (Note: Subjects with high IgM values or hyper-viscosity symptoms during screening may receive plasmapheresis prior to initiating study drug if the previous plasmapheresis was performed \>35 days before the plasmapheresis performed during screening (in order to obtain a true baseline IgM value for efficacy evaluations).
• Failure to have fully recovered (i.e., ≤Grade 1 toxicity) from the reversible effects of prior treatment for WM.
• Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) ≥470 msec.
• Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• History of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) defined by positive polymerase chain reaction (PCR).
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
• Major surgical procedure within ≤14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment, radiotherapy ≤14 days prior to initiating study treatment, systemic treatment within 14 days before the first dose of APG-2575.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (14)

City of Hope

Duarte, California, 91010, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Weill Cornell Univ Hospitals

New York, New York, 10065, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

St. Vincent Hospital

Melbourne, 3065, Australia

Location

Nanfang Hospital

Guangzhou, Guangdong, China

Location

Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Location

Beijing Chaoyang Hospital

Beijing, China

Location

The First Affiliated Hospital,College Of Medicine,Zhejiang University

Hangzhou, China

Location

The First Affiliated Hospital with Nanjing Medical University

Nanjing, China

Location

The First Affiliated Hospital Of Soochow University

Suzhou, China

Location

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Lisaftoclax

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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: APG2575 400 mg ramp up arm

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: May 30, 2021
• Primary Completion: February 5, 2024
• Study Completion: August 13, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

AU (1); CN (8); US (5)