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

Study Identifier:
APG3288XG101
CT.gov Identifier:
NCT07424833
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

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Study 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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
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Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: EXPERIMENTAL: Part 1 (Dose Escalation Phase)
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Drug: APG-3288 at multiple dose levels will be evaluated to determine the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD).
Drug: Drug: APG-3288
Drug: Orally administered daily; 28 days per cycle.
Drug: EXPERIMENTAL: Part 2 (Dose Expansion Phase)
Drug: Indications and dose cohorts to be determined from Part 1
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting

Requirements information
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 Age ≥ 18 years old.
  • ECOG≤1 or ECOG≤2.
  • Expected survival ≥ 3 months.
  • According to the World Health Organization (WHO) guidelines, it is defined as having a B-cell hematologic malignancy that has been confirmed by histology or cytology.
  • Previously received systematic treatment.
  • It has full organ function.
  • Male participants, female patients of childbearing potential, and their partners must agree to use effective contraception throughout the treatment period and for at least three months after the last dose of the study drug.
  • The candidate is able to understand the contents of the written informed consent form, is willing to sign the written informed consent form, and is willing and able to comply with the research procedures and follow-up examination requirements.
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 Currently receiving concurrent anti-tumor therapy; or receiving any experimental treatment within 14 days prior to the first administration of the investigational drug or within 5 half-lives of the corresponding investigational treatment (whichever is shorter).
  • The toxicity caused by previous radiotherapy, targeted therapy, immunotherapy or chemotherapy drugs persists and has not recovered to grade <2 (excluding hair loss or vitiligo).
  • Use therapeutic doses of anticoagulants or antiplatelet drugs; low doses of anticoagulants may be used to maintain the patency of central venous catheters.
  • The patient received biological growth factors within 7 days prior to the first administration of the study drug.
  • Patients who, according to the researchers' assessment, had not fully recovered from previous surgeries, or had undergone major surgery within 28 days prior to enrollment, or minor surgery within 14 days prior to enrollment, were included in the study.
  • He suffers from a serious heart condition.
  • Clinically active and uncontrolled symptomatic infections, including fungal, bacterial, and/or viral infections. Patients with well-controlled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections may be considered for inclusion.
  • Autoimmune diseases (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, etc.), active inflammatory bowel disease, chronic infection, or any other disease or condition associated with chronic inflammation.
  • Simultaneously use QT interval prolongation drugs.
  • History of torsades de pointes ventricular tachycardia.
  • Patients with known or suspected allergic or hypersensitivity reactions to drugs/compounds similar to APG-3288.
  • The researchers determined that there were any other circumstances or factors that would make the patient unsuitable to participate in this study.
  • In addition to the malignant tumor Disease of this study, patients also had other malignant diseases.
  • Researchers believe that serious and/or uncontrolled medical conditions may affect individual safety or impair the assessment of research results.
  • Subjects who are pregnant (confirmed by serum human chorionic gonadotropin [HCG] testing) or lactating.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START New Jersey
East Brunswick, NJ, United States, 08816
Investigator
Bruno Fang
Status
Will Be Recruiting
Condition(s) Treated at Site
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