Evaluating APG-115 and APG-2575 for T-Prolymphocytic Leukemia and Non-Hodgkin's Lymphoma

A Phase IIa Study Evaluating the Pharmacokinetics, Safety and Efficacy of APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With Relapsed/Refractory T-Cell Prolymphocytic Leukemia (R/R T-PLL) or Non-Hodgkin's Lymphoma (NHL).

This study is testing a new treatment using two drugs, APG-115 and APG-2575, to see if they can help people with relapsed or hard-to-treat T-Prolymphocytic Leukemia and Non-Hodgkin's Lymphoma feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT04496349 on ClinicalTrials.gov

What this trial studies

This phase IIa clinical trial aims to assess the pharmacokinetics, safety, and efficacy of APG-115, both as a standalone treatment and in combination with APG-2575, for patients with relapsed or refractory T-Prolymphocytic Leukemia (T-PLL) and Non-Hodgkin's Lymphoma (NHL). The study focuses on disrupting the interaction between the MDM2 oncoprotein and the tumor suppressor P53, which is expected to enhance P53 and P21 protein expression, leading to increased apoptosis in cancer cells. Participants will be monitored for safety and treatment response across multiple centers.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory T-PLL or NHL who have received at least one prior therapy.

Not a fit: Patients who have not had chemotherapy or antibody therapy for at least 7 days prior to starting the treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat T-PLL and NHL.

How similar studies have performed: Other studies targeting the MDM2-P53 interaction have shown promise, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years old
2. Patients with relapsed/refractory T-PLL who have active disease and have received at least one prior therapy; Patients with histologically confirmed diagnosis of NHL, NHL Patients must be either relapsed, refractory, intolerant, or are considered ineligible for therapies known to provide clinical benefit;
3. Patients must not have had chemotherapy or antibody therapy for 7 days prior to starting APG-115 and/or APG-2575. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
4. Absolute neutrophil count (ANC) ≥ 500/mm˄3; hemoglobin ≥ 60 g/L; platelet count ≥ 30,000/mm˄3
5. Patients with adequate organ function;
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
7. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his/her legally authorized representative is required prior to their enrollment on the protocol.

Exclusion Criteria:

1. Patient previously treated with a murine double minute 2 (MDM2) inhibitor.
2. Known active, uncontrolled central nervous system (CNS) malignancy
3. Patients require graft versus host therapy, or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose of study drug).
4. Patients who have any conditions or illness that, according to the opinions of the Investigators or the medical monitor, would compromise patient safety or interfere with the evaluation of safety and efficacy to the study drug(s).
5. Patients who have used strong CYP2C8 inhibitors, or moderate or strong CYP3A4 inhibitors or inducers within washout period of 14 days or 7 half-lives before the first administration of study drugs, whichever is longer.

Where this trial is running

Houston, Texas

• MD Anderson — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Genevieve Frank

Conditions T-Prolymphocytic Leukemia; Non-Hodgkins Lymphoma