In Part 1, 12-18 participants will be enrolled using a 3+3 dose escalation design. Patients receive APG-115 orally once every day (QD) with meal on Days 1 to 5, and 23 days off in the 28-day cycles.~In Part 2, patients receive APG-115 orally QD on Days 1 to 5, followed by 23 days off in a 28-day cycle. APG-115 dose escalation will use a standard 3+3 design starting from 150 mg, followed by 200 mg, then 250 mg. APG-2575 will be administered at 800 mg after ramp-up period. To prevent tumor lysis syndrome (TLS), APG-2575 needs to follow a 3-day daily ramp-up schedule from 200 mg before the fixed dose 800 mg is reached.
This is a multi-center, open-label, phase IIa study to evaluate the pharmacokinetics (PK), safety, and efficacy of APG-115 as a single agent or in combination with APG-2575 in patients with T-PLL. The study consists of two parts. A total of 24-36 T-PLL patients will be enrolled.