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

February 19, 2026 updated by: Ascentage Pharma Group Inc.

A Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of APG-3288 in Patients With Relapsed/Refractory Hematological Malignancies

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Part 1 (Dose Escalation Phase): Patients will receive orally administered APG-3288 at specified doses once daily in 28-day cycles. This phase aims to determine the MTD or RP2D of APG-3288 for patients who have failed standard therapy and for whom no standard therapy offering clinical benefit is available.

Part 2 (Dose Expansion Phase): Following the completion of Part 1, Part 2 will be initiated to further evaluate dose safety. Doses will be determined based on a comprehensive assessment of the pharmacokinetic (PK), pharmacodynamic (PD), safety, and efficacy data of APG-3288 from Part 1. In Part 2, up to 60 patients per chosen indication will be enrolled and randomly assigned in equal proportions to 2 or 3 dose cohorts to evaluate dose safety.

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China
        • Henan Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Keshu Zhou, M.D.,Ph.D.
  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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:

    1. New York Heart Association class III or IV cardiac disease, including pre-existing uncontrolled, clinically-significant arrhythmia, congestive heart failure, or cardiomyopathy.
    2. Unstable angina, myocardial infarction, or a coronary revascularization procedure within ≤ 3 months prior to initiation of study treatment.
    3. History of left ventricular ejection fraction < 50%.
    4. 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.
  • Concurrent malignancy other than the one being treated in this study with the exception of the following: cured malignancy without recurrence within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of any type.
  • Any severe and/or uncontrolled medical condition that, in the investigator's opinion, may compromise the individual's safety or the evaluation of study results.
  • Prior treatment with: BTK degrader treatment or allogeneic stem cell transplant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 (Dose Escalation Phase)
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
Orally administered daily; 28 days per cycle.
Experimental: Part 2 (Dose Expansion Phase)
Indications and dose cohorts to be determined from Part 1
Drug: APG-3288
Orally administered daily; 28 days per cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities (DLTs) at each dose level
Time Frame: From first dose through the end of Cycle 1 (e.g., Day 1 to Day 28)
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)
Time Frame: From first dose of study treatment through 30 days after the last dose
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
Time Frame: During the dose escalation phase (Part 1)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak plasma concentration (Cmax) of APG-3288
Time Frame: From first dose through 24 hours post-dose
The assessment of maximum observed plasma concentration (Cmax) following administration of APG-3288.
From first dose through 24 hours post-dose
Area Under the Plasma Concentration-Time Curve (AUC) of APG-3288
Time Frame: From first dose through last measurable concentration, assessed up to 24 hours post-dose
Area under the plasma concentration vs time curve (AUC0-t and AUC0-inf) of APG-3288 following administration APG-3288 at escalating dose levels.
From first dose through last measurable concentration, assessed up to 24 hours post-dose
Pharmacodynamic (PD) profile of APG 3288
Time Frame: From baseline of study treatment through 30 days after the last dose
The pharmacodynamic effects of APG 3288 will be evaluated by changes in Bruton's tyrosine kinase (BTK) levels from baseline over time during treatment.
From baseline of study treatment through 30 days after the last dose
Objective response rate (ORR)
Time Frame: From first dose until the first documented disease progression or end of treatment, assessed up to 24 months
ORR is defined as the proportion of patients who achieve partial response (PR) or better as assessed by the investigator at each efficacy assessment and upon disease progression or at end-of-treatment
From first dose until the first documented disease progression or end of treatment, assessed up to 24 months
Duration of response (DoR)
Time Frame: From the first documented response until disease progression or death, assessed up to 24 months
DoR is defined as duration in days from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease for responders (PR or better) as assessed by the investigator or death due to any cause, whichever occurs first.
From the first documented response until disease progression or death, assessed up to 24 months
Time to response (TTR)
Time Frame: From first dose until the first documented response, assessed up to 24 months
TTR is defined as the time interval from date of first dose of study drug to the date of initial documentation of a response (PR or better) as assessed by the investigator.
From first dose until the first documented response, assessed up to 24 months
Progression free survival (PFS)
Time Frame: From first dose until the first documented disease progression or death, whichever occurs first, assessed up to 24 months
PFS is defined as the time interval from date of first dose of study drug to the date of initial documentation of disease progression or death due to any cause, whichever occurs first, as assessed by the investigator.
From first dose until the first documented disease progression or death, whichever occurs first, assessed up to 24 months
Overall survival (OS)
Time Frame: From first dose until death from any cause, assessed up to 24 months
OS is defined as the time interval from date of first dose of study drug to the date of death due to any cause.
From first dose until death from any cause, assessed up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ascentage Pharma Group Inc.

Investigators

  • Principal Investigator: Keshu Zhou, M.D.,Ph.D., Henan Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

February 1, 2026

First Submitted That Met QC Criteria

February 19, 2026

First Posted (Actual)

February 20, 2026

Study Record Updates

Last Update Posted (Actual)

February 20, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APG3288XG101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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