A Study of APG-3288 in Relapsed/Refractory Blood Cancers

NCT07424833 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: APG3288XG101
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a Phase I, multicenter, open-label, two-stage study of APG-3288 monotherapy, aiming to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of APG-3288 administered orally once daily in patients with relapsed/refractory (R/R) hematologic malignancies.

Conditions

Relapsed/Refractory Hematological Malignancies; Relapsed/Refractory Mantle Cell Lymphoma (MCL); Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL; Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL; Including Richter Transformation); Relapsed/Refractory Waldenström Macroglobulinemia (WM); Relapsed/Refractory Marginal Zone Lymphoma (MZL); Relapsed/Refractory Follicular Lymphoma (FL)

Keywords

Relapsed/Refractory Hematological Malignancies; APG-3288

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicities (DLTs) at each dose level

  A DLT is defined as any treatment-related adverse event (TRAE) meeting protocol-specified toxicity criteria occurring during the DLT evaluation period (Cycle 1). DLTs will be assessed in participants receiving escalating dose levels of APG-3288 to evaluate its safety and tolerability.

  From first dose through the end of Cycle 1 (e.g., Day 1 to Day 28)

• Incidence of treatment emergent adverse events (TEAEs)

  The incidence of treatment emergent adverse events (TEAEs), including Grade 3-5 TEAEs, serious adverse events (SAEs), TEAEs leading to dose interruption, dose reduction, or treatment discontinuation, and deaths, will be assessed in participants receiving APG-3288 in Part 1 (dose escalation) and Part 2 (dose expansion) of the study.

  From first dose of study treatment through 30 days after the last dose

• Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of APG 3288

  The MTD and/or RP2D of APG-3288 will be determined during the dose escalation phase based on the incidence of DLTs, overall safety, tolerability, and available pharmacokinetic and pharmacodynamic data.

  During the dose escalation phase (Part 1)

Secondary Outcomes (8)

• Peak plasma concentration (Cmax) of APG-3288

  From first dose through 24 hours post-dose

• Area Under the Plasma Concentration-Time Curve (AUC) of APG-3288

  From first dose through last measurable concentration, assessed up to 24 hours post-dose

• Pharmacodynamic (PD) profile of APG 3288

  From baseline of study treatment through 30 days after the last dose

• Objective response rate (ORR)

  From first dose until the first documented disease progression or end of treatment, assessed up to 24 months

• Duration of response (DoR)

  From the first documented response until disease progression or death, assessed up to 24 months

Study Arms (2)

Part 1 (Dose Escalation Phase)

EXPERIMENTAL

APG-3288 at multiple dose levels will be evaluated to determine the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD).

Drug: APG-3288

Part 2 (Dose Expansion Phase)

EXPERIMENTAL

Indications and dose cohorts to be determined from Part 1

Drug: APG-3288

Interventions

APG-3288 DRUG

Orally administered daily; 28 days per cycle.

Part 1 (Dose Escalation Phase); Part 2 (Dose Expansion Phase)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) status ≤ 1 in Part 1 (dose escalation), and ≤ 2 in Part 2 (dose expansion).
• Part 1 (Dose Escalation): histologically or cytologically confirmed diagnosis of R/R CLL/SLL, DLBCL (including Richter Transformation), MCL, WM, MZL, or FL.
• Prior systemic therapy: at least 2 prior lines of systemic therapy (including BTK inhibitor for approved indications) and who have failed or are not eligible for available therapies with established clinical benefit.
• Measurable disease per response criteria specific to the malignant condition.
• Adequate organ and bone marrow function.

You may not qualify if:

• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogs, agonists required to suppress serum testosterone levels).
• Any investigational therapy within 14 days prior to the first dose of study drug or within 5 half-lives of the respective investigational drug (whichever is shorter).
• Persistent toxicities from prior radiotherapy, targeted therapy, immunotherapy, or chemotherapy agents that have not recovered to Grade \<2 (except for alopecia or vitiligo).
• Symptomatic brain metastases due to tumor involvement of the central nervous system (CNS). Patients with CNS tumors who have been treated, are asymptomatic, and who have discontinued steroids (for the treatment of CNS tumors) for \> 28 days may be enrolled.
• Use of therapeutic-dose anticoagulants or antiplatelet agents. (Use of low-dose anticoagulants to maintain central venous catheter patency is permitted)
• Biological growth factors within 7 days prior to the first dose of study drug.
• Patients who, in the investigator's judgment, have not adequately recovered from prior surgery, or have undergone major surgery within 28 days prior to enrollment, or minor surgery within 14 days prior to enrollment.
• Significant cardiac disease defined as:
• New York Heart Association class III or IV cardiac disease, including pre-existing uncontrolled, clinically-significant arrhythmia, congestive heart failure, or cardiomyopathy.
• Unstable angina, myocardial infarction, or a coronary revascularization procedure within ≤ 3 months prior to initiation of study treatment.
• History of left ventricular ejection fraction \< 50%.
• Poorly controlled hypertension, or history of poor compliance with antihypertensive drug regimens.
• Clinically active and uncontrolled symptomatic infection; well-controlled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection may be considered for enrollment.
• Autoimmune diseases, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
• Concurrent use of QT-prolonging medications or history of torsades de pointes.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (2)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Recurrence; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• Keshu Zhou, M.D.,Ph.D.

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yifan Zhai, M.D., Ph.D.

CONTACT

18998334688; Yzhai@ascentage.com

Qiwei Chen, M.D.

CONTACT

Qiwei.Chen@ascentage.com

Study Design

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

Study Record Dates

• First Submitted: February 1, 2026
• First Posted: February 20, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); US (1)