Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
APG-115 · 6 trials · 17 indications
To evaluate the safety of APG-115 as a single agent
To evaluate the maximum tolerated dose of APG-115 and APG-2575 in combination
DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 3 weeks of study treatment. These will be assessed via CTCAE version 5.0.
Number of patients with adverse event; Number of patients with abnormal vital signs, abnorma physical examination, laboratory abnormalities, and abnormal 12-lead ECG in monotherapy of APG-115 and combined with APG-2575.
Phase I is aimed to generate data to select the recommended Phase II dose.
Phase II is to assess overall response rate of APG-115 in combination with toripalimab defined as the percentage of subjects with a best overall confirmed CR or a PR at any time as per RECIST v1.1.
DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5) by organ system. DLT will be defined as clinically significant drug-related adverse events during the Cycle one.
Part I is to assess the safety and tolerability of APG-115 by assessing the dose-limiting toxicity (DLT) of APG-115 in combination with pembrolizumab. End points included: Incidence of DLTs during the first 3 weeks of treatment of each dose cohort; Severity and frequency of any adverse event(s) (AE) and serious adverse event(s) (SAE) based on NCI CTCAE 5.0
Phase II is to assess overall response rate of APG-115 as monotherapy and in combination with pembrolizumab defined as the percentage of subjects with a best overall confirmed complete response (CR) or a partial response (PR) at any time as per RECIST 1.1
Patients with APG-115 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0
| Arm | Type | Description |
|---|---|---|
| APG-115 monotherapy part | EXPERIMENTAL | APG-115 will be given alone |
| APG-115 + APG-2575 combination dose escalation part | EXPERIMENTAL | APG-115 is given in combination with APG-2575 |
| APG-115 + APG-2575 combination dose expansion part | EXPERIMENTAL | APG-115 is given in combination with APG-2575 |
| APG-115 monotherapy in part1 | EXPERIMENTAL | Multiple dose cohorts, to determine the RP2D of APG-115. |
| APG-115 combined with APG-2575 in part2 | EXPERIMENTAL | Multiple dose cohorts of APG-2575, to determine the RP2D of APG-2575 combined with APG-115. |
| APG-115+Toripalimab | EXPERIMENTAL | - |
| APG-115/APG-115+Cytarabine in Relapse/Refractory AML | EXPERIMENTAL | - |
| APG-115/APG-115+Aza in relapsed/progressed high risk MDS | EXPERIMENTAL | - |
| APG-115+pembrolizumab open label, two-part phase Ib/II | EXPERIMENTAL | single arm dose escalation and dose expansion |
| APG-115 | EXPERIMENTAL | APG-115 to be explored sequentially during accelerated dose escalation. This will continue until either the occurrence in Cycle 1 of one DLT or two Grade 2 toxicities (graded as per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.0) that are related or possibly related to APG-115. When either of these criteria is fulfilled, dose escalation will be converted to a standard 3+3 escalation scheme, |
| Name | Type | Description |
|---|---|---|
| APG-115 | DRUG | QOD, 2 weeks on, 1 week off, in repeated 21-day cycles |
| APG-2575 | DRUG | APG-2575 given orally each day in cycle, in repeated 21-day cycles |
| Toripalimab | DRUG | Toripalimab is administrated following CDE approved label dose, i.e.: 240 mg intravenous infusion at Day 1 of every 3 weeks as a cycle. |
| Azacitidine | DRUG | 75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle) |
| Cytarabine | DRUG | 1g/m\^2 IV QD on Days 3-7 (28-day cycle) |
| Phase 1b: APG-115+pembrolizumab | DRUG | dose escalation of APG-115 in combination with label dose of pembrolizumab, Four dose levels of APG-115 will be tested: 50, 100, 150, and 200 mg. APG-115 will be administrateddose escalation of APG-115 in combination with label dose of pembrolizumab, Fourfour dose levels of APG-115 will be tested: 50, 100, 150, and 200 mg. APG-115 will be administrated orally every other day (QOD) for consecutive 2 weeks (ie. dosed at Day 1, 3, 5, 7, 9, 11, and 13), with one week dosing off as there are cycles every 3-weeks a cycle. Pembrolizumab is administrated following FDA approved label dose, i.e., 200 mg intravenous infusion at Day 1 of every 3 weeks as a cycle. Phase II: Combination of APG-115 at 150 mg (RP2D) and pembrolizumab or APG-115 monotherapy alone. |
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 ineligi...
APG-115 is an investigational small molecule oncology drug developed by Ascentage Pharma Group International. It is being studied in several cancers, including acute myeloid leukemia, liposarcoma, neuroblastoma, T-prolymphocytic leukemia, melanoma, and advanced solid tumors or lymphoma. It is given both as a single agent and in combination with other therapies in clinical trials.
APG-115 targets the MDM2-p53 interaction and acts as an inhibitor. By blocking MDM2, the drug is designed to interfere with MDM2-mediated suppression of the p53 tumor suppressor pathway. This mechanism is being explored across the solid tumor and hematologic cancer indications in its clinical program.
APG-115 is developed by Ascentage Pharma Group International, whose American Depositary Shares trade under the ticker AAPG. The company is running the clinical program for the drug across multiple cancer types in China and the United States.
APG-115 is in Phase 1 clinical development and is investigational. It has not been approved for any indication. Its trials include Phase 1 studies in neuroblastoma, solid tumors, liposarcoma, acute myeloid leukemia, and myelodysplastic syndromes, plus a Phase 2 study in relapsed or refractory T-prolymphocytic leukemia and non-Hodgkin lymphoma.
APG-115 is being studied in NCT05701306 in recurrent or refractory neuroblastoma and solid tumors, NCT04785196 in advanced liposarcoma and advanced solid tumors, NCT04496349 in relapsed or refractory T-prolymphocytic leukemia and non-Hodgkin lymphoma, and NCT04275518 in acute myeloid leukemia and myelodysplastic syndromes. All four trials are currently recruiting.