Relapsed/Refractory Hematological MalignanciesPhase 1NCT07424833
A Study of APG-3288 in Relapsed/Refractory Blood Cancers
A Phase 1 study testing APG-3288 in people with Relapsed/Refractory Hematological Malignancies and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL, run by Ascentage Pharma Group Inc. at 6 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Hematological Malignancies, Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL, Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL; Including Richter Transformation)
- What is being tested?
- APG-3288
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 10 Mar 2026to Dec 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- 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
Trial locations and contacts
6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Qiwei Chen, M.D. contact
6 sites in 2 countries
United States5 sites, 5 recruiting
- Recruiting
START New Jersey
East Brunswick, New Jersey, 08816
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
- Not yet recruiting
The University of TX MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Mayo Clinic
Jacksonville, Florida, 32224
- Recruiting
START Los Angele
Los Angeles, California, 90025
China1 site, 1 recruiting
- Recruiting
Henan Cancer Hospital
Zhengzhou, Henan
Keshu Zhou, M.D.,Ph.D., 13674902391, dr_zkshu23810@163.com
Keshu Zhou, M.D.,Ph.D.
About this study
Official title: 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.
Read the 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.
- Conditions
- Relapsed/Refractory Hematological Malignancies, Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL, Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL; Including Richter Transformation), Relapsed/Refractory Mantle Cell Lymphoma (MCL), Relapsed/Refractory Waldenström Macroglobulinemia (WM), Relapsed/Refractory Marginal Zone Lymphoma (MZL)
- Being tested
- APG-3288
- Keywords
- Relapsed/Refractory Hematological Malignancies, APG-3288
- Medical subject headings
- Hematologic Neoplasms, Recurrence, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-3288Drug
Orally administered daily; 28 days per cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: APG-3288 |
| Part 2 (Dose Expansion Phase) | Experimental | Indications and dose cohorts to be determined from Part 1 Receives: Drug: APG-3288 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: During the dose escalation phase (Part 1)
Secondary outcomes (8)
Peak plasma concentration (Cmax) of APG-3288
The assessment of maximum observed plasma concentration (Cmax) following administration of APG-3288.
Measured: From first dose through 24 hours post-dose
Area Under the Plasma Concentration-Time Curve (AUC) of APG-3288
Area under the plasma concentration vs time curve (AUC0-t and AUC0-inf) of APG-3288 following administration APG-3288 at escalating dose levels.
Measured: From first dose through last measurable concentration, assessed up to 24 hours post-dose
Pharmacodynamic (PD) profile of APG 3288
The pharmacodynamic effects of APG 3288 will be evaluated by changes in Bruton's tyrosine kinase (BTK) levels from baseline over time during treatment.
Measured: From baseline of study treatment through 30 days after the last dose
Objective response rate (ORR)
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
Measured: From first dose until the first documented disease progression or end of treatment, assessed up to 24 months
Duration of response (DoR)
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.
Measured: From the first documented response until disease progression or death, assessed up to 24 months
Time to response (TTR)
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.
Measured: From first dose until the first documented response, assessed up to 24 months
Progression free survival (PFS)
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.
Measured: From first dose until the first documented disease progression or death, whichever occurs first, assessed up to 24 months
Overall survival (OS)
OS is defined as the time interval from date of first dose of study drug to the date of death due to any cause.
Measured: From first dose until death from any cause, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start10 Mar 2026
- Primary completionDec 2029 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Hematological MalignanciesStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keshu Zhou, M.D.,Ph.D., Principal investigator, Henan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07424833
- Sponsor's protocol ID
- APG3288XG101
- Status last verified
- Oct 2026
- First submitted
- 1 Feb 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of APG-3288 in Patients With Relapsed/Refractory Hematological Malignancies
- ClinicalTrials.gov ID
- NCT07424833
- Acronym / sponsor ID
- APG3288XG101
- Conditions
- Relapsed/Refractory Hematological Malignancies, Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL, Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL; Including Richter Transformation), Relapsed/Refractory Mantle Cell Lymphoma (MCL), Relapsed/Refractory Waldenström Macroglobulinemia (WM), Relapsed/Refractory Marginal Zone Lymphoma (MZL)
- Keywords
- Relapsed/Refractory Hematological Malignancies, APG-3288
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Mar 2026 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 20 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 (Dose Escalation Phase) | Experimental | Drug: APG-3288APG-3288 at multiple dose levels will be evaluated to determine the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD). |
| Part 2 (Dose Expansion Phase) | Experimental | Drug: APG-3288Indications and dose cohorts to be determined from Part 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APG-3288Orally administered daily; 28 days per cycle. | Drug | Part 1 (Dose Escalation Phase), Part 2 (Dose Expansion Phase) |
Primary outcome
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.
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.
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.
8 secondary outcomes
Peak plasma concentration (Cmax) of APG-3288
Time frame: 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
Pharmacodynamic (PD) profile of APG 3288
Time frame: 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
Duration of response (DoR)
Time frame: 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
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
Overall survival (OS)
Time frame: From first dose until death from any cause, assessed up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Qiwei Chen, M.D. contact
Keshu Zhou, M.D.,Ph.D. principal investigator
Henan Cancer Hospital
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APG-3288 in people with Relapsed/Refractory Hematological Malignancies and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL, run by Ascentage Pharma Group Inc. at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yifan Zhai, M.D., Ph.D. (18998334688, Yzhai@ascentage.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.