Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
APG-115 · 5 trials · 9 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.
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 | 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) |
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 being studied in patients with advanced solid tumors or lymphoma, acute myeloid leukemia (AML), T-prolymphocytic leukemia, liposarcoma, and neuroblastoma. It is in Phase 1 clinical development for these oncology indications.
APG-115 targets the MDM2-p53 interaction. It is an inhibitor of MDM2, a protein that regulates the tumor suppressor p53. By inhibiting MDM2, APG-115 aims to reactivate p53 function in cancer cells.
APG-115 is being developed by Ascentage Pharma Group International, whose American Depository Shares trade under the ticker AAPG. The company is conducting Phase 1 clinical trials of APG-115 across multiple oncology indications.
APG-115 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Multiple Phase 1 trials are ongoing or completed to evaluate its safety and efficacy in various cancers.
APG-115 is being studied in several Phase 1 trials, including NCT02935907 in advanced solid tumors or lymphomas, NCT04275518 in AML and myelodysplastic syndromes, NCT04785196 in liposarcoma or advanced solid tumors combined with a PD-1 inhibitor, and NCT05701306 in neuroblastoma or solid tumors alone or with APG-2575.
APG-115 is also known as alrizomadlin. It is an MDM2-p53 inhibitor being developed by Ascentage Pharma for the treatment of various cancers, including solid tumors, lymphomas, and leukemias.