A Study Evaluating APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With R/R T-PLL and NHL

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).

The goal of this study is to evaluate the pharmacokinetics (PK), safety, and efficacy of APG-115 as a single agent or in combination with APG-2575 in patients with T-PLL and NHL.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkins Lymphoma; T-Prolymphocytic Leukemia
• Intervention / Treatment: Drug: APG-115; Drug: APG-2575

Detailed Description

This is a phase IIa, open-label, multi-center, clinical trial of interfering the binding of MDM2 oncoprotein with the tumor suppressor P53 protein, leads to increased P53 and P21 protein expression and activates P53-mediated apoptosis. The hypothesis is that APG-115 monotherapy and in combination with APG-2575 will shows good safety and efficacy in patients with R/R T-PLL and NHL

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jocelyn Budzynski; Phone Number: 301-693-6952; Email: jocelyn.budzynski@ascentage.com
• Study Contact Backup: Name: Genevieve Frank; Phone Number: 301-802-3659; Email: genevieve.frank@ascentage.com

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson
      • Contact: Kelly Quagliato; Phone Number: 713-614-2069; Email: krquagliato@mdanderson.org
      • Principal Investigator: Tapan Kadia, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APG-115 monotherapy part; APG-115 will be given alone	Drug: APG-115; QOD, 2 weeks on, 1 week off, in repeated 21-day cycles
Experimental: APG-115 + APG-2575 combination dose escalation part; APG-115 is given in combination with APG-2575	Drug: APG-115; QOD, 2 weeks on, 1 week off, in repeated 21-day cycles; Drug: APG-2575; APG-2575 given orally each day in cycle, in repeated 21-day cycles
Experimental: APG-115 + APG-2575 combination dose expansion part; APG-115 is given in combination with APG-2575	Drug: APG-115; QOD, 2 weeks on, 1 week off, in repeated 21-day cycles; Drug: APG-2575; APG-2575 given orally each day in cycle, in repeated 21-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose of APG-115	To evaluate the safety of APG-115 as a single agent	21 days
Maximum tolerated dose of APG-115+APG-2575	To evaluate the maximum tolerated dose of APG-115 and APG-2575 in combination	21 days

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Investigators: Study Chair: Yifan Zhai, MD, PhD, Ascentage Pharma Group Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 3, 2020

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell; Hemic and Lymphatic Diseases; Leukemia, Prolymphocytic; Lymphoma, Non-Hodgkin; Leukemia, Prolymphocytic, T-Cell; Lisaftoclax
• Other Study ID Numbers: APG115TU101

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