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Also known as [14C ]APG-2575, APG-2575(Lisaftoclax )
APG-2575 · 6 trials · 6 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.
ORR is defined by Complete Remission (CR)+ CR with incomplete marrow recovery (CRi) + Partial Remission (PR) (according to NCI-WG CLL(2018)) and by CR+PR ( according to Lugano (2014)).Response will be evaluated every 2 cycles (8 weeks) till complete treatment or one month after last dose.
According to CTCAE v5.0, the number and frequency of adverse events of test drug were assessed.
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
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
MTD/RP2D will be determined based on DLTs observed during cycle one.
Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 5.0
| Arm | Type | Description |
|---|---|---|
| APG-2575 (Lisaftoclax) combined with Azacitidine | EXPERIMENTAL | - |
| Placebo combined with Azacitidine | ACTIVE_COMPARATOR | - |
| APG-2575 single agent in Relapse/Refractory CLL/SLL | EXPERIMENTAL | APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle. |
| APG-2575 | EXPERIMENTAL | Dose escalation |
| Placebo | PLACEBO_COMPARATOR | - |
| APG2575 400 mg | EXPERIMENTAL | APG2575 400mg ramp up arm |
| APG2575 600 mg | EXPERIMENTAL | APG2575 600 mg ramp up arm |
| APG2575 800 mg arm | EXPERIMENTAL | APG2575 800 mg arm ramp up |
| APG-2575+Rituximab in Relapse/Refractory CLL/SLL | EXPERIMENTAL | Stage 1:APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg. Rituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1. Every 28 days as a cycle. Stage 2: APG-2575 MTD/RP2D combined with rituximab. Every 28 days as a cycle. |
| APG-2575+ibrutinib in Relapse/Refractory CLL/SLL | EXPERIMENTAL | Stage 1: APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg.Ibrutinib 420mg orally once daily during C1D8-28 and following cycles. Every 28 days as a cycle. Stage 2: APG-2575 MTD/RP2D combined with ibrutinib. Every 28 days as a cycle. |
| single-agent, open-label, Phase I study of APG-2575 | EXPERIMENTAL | The study consists of the dose escalation stage and the dose expansion stage |
| Name | Type | Description |
|---|---|---|
| APG-2575(Lisaftoclax ) | DRUG | QD, oral administration, every 28 days for a dosing cycle. |
| Placebo | OTHER | QD, oral administration, every 28 days for a dosing cycle. |
| Azacitidine Injection | DRUG | QD, subcutaneous or intravenous injection, D1-7 in 28-day cycle. |
| APG2575 | DRUG | APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle. |
| APG-2575 | DRUG | Take orally once daily (QD) for 12 weeks. |
| APG2575 400 mg | DRUG | APG2575 400 mg |
| APG2575 600 mg | DRUG | APG2575 600 mg |
| APG2575 800 mg | DRUG | APG2575 800 mg |
| Rituximab | DRUG | Rituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1. |
| Ibrutinib | DRUG | Ibrutinib 420mg orally once daily during C1D8-28 and following cycles. |
Inclusion Criteria: 1. Patients must have newly diagnosed AML that meets the criteria for acute myeloid leukemia (AML) and ineligible for standard chemotherapy. 2. Life expectancy of ≥3 months. 3. Be able to accept oral administration. 4. Patients aged ≥70 years with ECOG score of 0-2, or those age...
APG-2575 is an investigational small molecule BCL2 inhibitor being developed by Ascentage Pharma for blood cancers and autoimmune disease. It is in Phase 3 development for acute myeloid leukemia and is also being studied in chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, and systemic lupus erythematosus.
APG-2575 is being studied in acute myeloid leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom macroglobulinemia, and systemic lupus erythematosus. It is investigational and has not been approved for any indication. The most advanced program is a Phase 3 trial in acute myeloid leukemia combining APG-2575 with azacitidine.
APG-2575 targets BCL2, a protein that helps cancer cells avoid apoptosis, or programmed cell death. APG-2575 is a BCL2 inhibitor, meaning it blocks this protein to promote death of malignant cells. This mechanism is relevant across B-cell malignancies such as chronic lymphocytic leukemia and acute myeloid leukemia.
APG-2575 is being developed by Ascentage Pharma Group International, whose American Depositary Shares trade under the ticker AAPG. Ascentage is the sponsor of the clinical trials evaluating APG-2575 in acute myeloid leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, and systemic lupus erythematosus.
APG-2575 is in Phase 3 development. The pivotal Phase 3 trial, NCT06389292, evaluates APG-2575 combined with azacitidine in acute myeloid leukemia and is currently recruiting. Earlier-stage trials include a Phase 2 study in relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma and a Phase 1 study in systemic lupus erythematosus.
APG-2575 is being evaluated in several trials. NCT06389292 is a Phase 3 study with azacitidine in acute myeloid leukemia. NCT05147467 is a Phase 2 study in relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. NCT04494503 is a Phase 1 study in the same blood cancers, and NCT06182969 is a Phase 1 study in systemic lupus erythematosus.
Yes, APG-2575 is also known as lisaftoclax. Other names used for the same compound include APG2575 and APG2575 400 mg. Lisaftoclax is the international nonproprietary name for this BCL2 inhibitor, so searches for either name refer to the same investigational drug.