Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Lisaftoclax (APG-2575)
Lisaftoclax · 5 trials · 4 indications
The primary endpoint was overall survival (OS), defined as the time from the date of randomization to the date of death of any cause.
PFS is defined as the time from randomization to disease progression(PD) or death from any cause.
To evaluate the progression-free survival (PFS) of lisaftoclax in combination with BTKi compared with BTKi monotherapy in CLL/SLL patients previously treated with BTKi as determined by independent radiological review committee (IRC) using the iwCLL guidelines
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during cycle one.
MTD/RP2D will be determined based on DLTs observed during cycle one.
DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0
MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment
| Arm | Type | Description |
|---|---|---|
| Lisaftoclax (APG-2575) combined with Azacitidine | EXPERIMENTAL | - |
| Placebo combined with Azacitidine | ACTIVE_COMPARATOR | Drug: azacitidine injection QD: hypodermic or intravenous injection |
| Lisaftoclax (APG-2575) combined with Acalabrutinib | EXPERIMENTAL | Lisaftoclax (APG-2575) 600 mg daily plus acalabrutinib 100 mg twice daily for a fixed duration of treatment up to 18 cycles. |
| Immunochemotherapy regimens | ACTIVE_COMPARATOR | FCR: Fludarabine: intravenously infused at 25 mg/m2 /d on Days 1 to 3 of Cycles 1-6 cyclophosphamide: intravenously infused at 250 mg/m2 /d on Days 1 - 3 of Cycles 1 - 6; rituximab: intravenously infused at 375 mg/m2 on C1D1, and at 500 mg/m2 on Day 1 of Cycles 2 - 6. F or R-Clb: Chlorambucil: orally administrated at 0.5 mg/kg on Days 1 and 15 of Cycles 1-6; rituximab: intravenously infused at 375 mg/m2 on C1D1, and at 500 mg/m2 on Day 1 of Cycles 2 - 6. |
| Arm 1 | ACTIVE_COMPARATOR | Combination therapy |
| Arm 2 | ACTIVE_COMPARATOR | mono therapy |
| Lisaftoclax (APG-2575) single agent | EXPERIMENTAL | Lisaftoclax (APG-2575) orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg, to determine the MTD/RP2D. |
| Lisaftoclax (APG-2575)+reduced-dose HHT | EXPERIMENTAL | Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with reduced-dose HHT in R/R AML, MPAL, BPDCN, CMML. |
| Lisaftoclax (APG-2575)+ standard-dose HHT | EXPERIMENTAL | Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with standard-dose HHT in R/R AML, MPAL, BPDCN, CMML. |
| Lisaftoclax (APG-2575)+ AZA | EXPERIMENTAL | Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in R/R AML, MPAL, BPDCN, CMML. |
| Lisaftoclax (APG-2575)+ AZA(HR-MDS.) | EXPERIMENTAL | Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in HR-MDS. |
| Lisaftoclax (APG-2575)+ AZA(Naïve AML.) | EXPERIMENTAL | Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in treatment naïve AML. |
| Lisaftoclax (APG-2575)+AZA+Olverembatinib | EXPERIMENTAL | Lisaftoclax (APG-2575) combines with AZA and Olverembatinib in R/R AML. |
| Lisaftoclax (APG-2575)+HHT+Olverembatinib | EXPERIMENTAL | Lisaftoclax (APG-2575) combines with HHT and Olverembatinib in R/R AML. |
| Lisaftoclax 400mg | EXPERIMENTAL | Lisaftoclax 400mg ramp up |
| Lisaftoclax 600mg | EXPERIMENTAL | Lisaftoclax 600mg ramp up |
| Lisaftoclax 800mg | EXPERIMENTAL | Lisaftoclax 800mg ramp up |
| Lisaftoclax 1000mg | EXPERIMENTAL | Lisaftoclax 1,000mg ramp up |
| Name | Type | Description |
|---|---|---|
| Lisaftoclax (APG-2575) | DRUG | QD, oral administration. |
| Azacitidine Injection | DRUG | QD, hypodermic or intravenous injection. |
| Placebo | OTHER | QD, oral administration. |
| Acalabrutinib | DRUG | BID, oral administration, every 28 days for a dosing cycle. |
| Fludarabine | DRUG | Every 28 days for a treatment cycle, administration of 6 cycles. |
| Cyclophosphamide，CTX | DRUG | Every 28 days for a treatment cycle, administration of 6 cycles. |
| Rituximab | DRUG | Every 28 days for a treatment cycle, administration of 6 cycles. |
| Chlorambucil | DRUG | Every 28 days for a treatment cycle, administration of 6 cycles. |
| lisaftoclax +BTK inhibitor | DRUG | lisaftolax + BTK inhibitor |
| BTK inhibitor | DRUG | BTK inhibitor |
| Reduced-dose HHT | DRUG | 1mg IV QD on Days 1-14 (28-day cycle). |
| standard-dose HHT | DRUG | 2mg/m\^2 IV QD on Days 1-7 (28-day cycle). |
| Azacitidine | DRUG | 75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle). |
| olverembatinib | DRUG | orally, with meals, QOD, every 28 days as a cycle. |
| Lisaftoclax | DRUG | Lisaftoclax investigation drug in ramp up dosing |
Inclusion Criteria: 1. Newly diagnosed higher-risk MDS. 2. ECOG score of ≤2. 3. Expected survival ≥ 3 months. 4. Adequate organ function. 5. Female subjects of potential childbearing potential have a negative urine or serum pregnancy test before dosing. Subjects of childbearing potential as well as...
Lisaftoclax is an investigational small molecule being studied in hematologic malignancies, including chronic lymphocytic leukemia and small lymphocytic lymphoma, higher-risk myelodysplastic syndrome, and relapsed or refractory acute myeloid leukemia. It is not yet approved and remains in clinical development.
Lisaftoclax targets Bcl-2, a protein that regulates apoptosis. By inhibiting Bcl-2, lisaftoclax is designed to restore the programmed cell death pathway in malignant cells. It is being evaluated both as a single agent and in combination with other therapies such as BTK inhibitors and azacytidine.
Lisaftoclax is being developed by Ascentage Pharma Group International, whose American Depositary Shares trade under the ticker AAPG. The company is running global Phase 3 trials for lisaftoclax in CLL/SLL and higher-risk myelodysplastic syndrome, as well as earlier-stage studies in acute myeloid leukemia.
Lisaftoclax is in Phase 3 clinical development. Three Phase 3 trials are currently recruiting: GLORA-4 in higher-risk myelodysplastic syndrome, a study combining lisaftoclax with acalabrutinib in newly diagnosed CLL/SLL, and a global CLL/SLL trial. A Phase 1 study in relapsed or refractory AML is also ongoing.
Lisaftoclax is being studied in four recruiting trials. Phase 3 trials include NCT06641414 in higher-risk myelodysplastic syndrome, NCT06319456 in newly diagnosed CLL/SLL, and NCT06104566 in CLL/SLL. A Phase 1 trial, NCT04501120, evaluates lisaftoclax alone and in combination in relapsed or refractory AML.
Yes, lisaftoclax is also known as APG-2575. The names refer to the same investigational Bcl-2 inhibitor. It is also described in combination regimens such as lisaftoclax plus a BTK inhibitor, reflecting its use alongside other agents in clinical trials.