NCT04275518

A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.

A Phase Ib Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of APG-115 as a Single Agent or in Combination With Azacitidine or Cytarabine in Patients With Relapse/Refractory AML and Relapsed/Progressed High/Very High Risk MDS

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 102 (estimated)
• Sponsor: Ascentage Pharma Group Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Acute myeloid leukemia is a malignant disorder characterized by the rapid, uncontrolled proliferation of malignant clonal hematopoietic stem cells that accumulate as immature, undifferentiated cells (blasts) in the bone marrow and circulation. APG-115 is a potent and orally active small-molecule MDM2 inhibitor, it binds to MDM2 protein and shows potent cell growth inhibitory activity in vitro with low nanomolar potencies in a subset of human cancer cell lines. APG-115 has demonstrated its strong antitumor activities with either daily or less frequent dosing-schedules in the acute leukemia xenograft models. This is a phase 1b, open-label, three-stages study that will initially evaluate the safety and PK/PD profile of APG-115 as a single agent, followed by a combination of APG-115 + azacytidine or cytarabine in R/R AML or MDS subjects. Patients will continue treatment for maximally 6 cycles or until progression of disease or unacceptable toxicity is observed or administrative discontinuation whichever occurs first. Patients who continue to be benefit after 6 cycles' treatment will receive additional cycles of treatment until progression of disease, unacceptable toxicity is observed or administrative discontinuation. (As long as it is proven safe).

Detailed description

Stage 1: This will be a 3+3 dose escalation to determine the DLTs and MTD/RP2D of APG-115 given according to the different dose levels once daily from Days 1 to 7 every 28 days. Stage 2: After stage 1 of APG-115 single agent dose escalation first cycle is completed, stage 2 can be initiated with the combination regimen. This will be a 3+3 dose escalation to determine the MTD/RP2D and DLTs of APG-115 + AZA(arm A)/Cytarabine (arm B)combination. Stage 3: dose expansion of the combination regimes.

Conditions

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndromes (MDS)

Interventions

Type	Name	Description
DRUG	APG-115	APG-115 orally once daily from Days 1 to 7 every 28 days.
DRUG	Azacitidine	75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle)
DRUG	Cytarabine	1g/m\^2 IV QD on Days 3-7 (28-day cycle)

Timeline

• Start date: 2020-07-06
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2020-02-19
• Last updated: 2024-10-15

Locations

14 sites across 1 country: China