A Study Evaluating APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With R/R T-PLL and NHL
- Conditions
- Non-Hodgkins LymphomaT-Prolymphocytic Leukemia
- Interventions
- Registration Number
- NCT04496349
- Lead Sponsor
- Ascentage Pharma Group Inc.
- Brief Summary
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.
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 78
- Age ≥ 18 years old
- 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;
- 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.
- Absolute neutrophil count (ANC) ≥ 500/mm˄3; hemoglobin ≥ 60 g/L; platelet count ≥ 30,000/mm˄3
- Patients with adequate organ function;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
- 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.
- Patient previously treated with a murine double minute 2 (MDM2) inhibitor.
- Known active, uncontrolled central nervous system (CNS) malignancy
- 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).
- 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).
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description APG-115 monotherapy part APG-115 APG-115 will be given alone APG-115 + APG-2575 combination dose escalation part APG-115 APG-115 is given in combination with APG-2575 APG-115 + APG-2575 combination dose escalation part APG-2575 APG-115 is given in combination with APG-2575 APG-115 + APG-2575 combination dose expansion part APG-115 APG-115 is given in combination with APG-2575 APG-115 + APG-2575 combination dose expansion part APG-2575 APG-115 is given in combination with APG-2575
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of APG-115 21 days To evaluate the safety of APG-115 as a single agent
Maximum tolerated dose of APG-115+APG-2575 21 days To evaluate the maximum tolerated dose of APG-115 and APG-2575 in combination
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
Ohio State University
🇺🇸Columbus, Ohio, United States
MD Anderson
🇺🇸Houston, Texas, United States
City of Hope
🇺🇸Duarte, California, United States