NCT04354727

A Study of APG-1252 in Patients With Myelofibrosis Who Progressed After Initial Therapy

Phase Ib/II Study of APG-1252 in Patients With Myelofibrosis Who Progressed After Initial Therapy

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Ascentage Pharma Group Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study is a designed to evaluate safety and activity of APG-1252 when administered as monotherapy and in combination with ruxolitinib in previously ruxolitinib treated myelofibrosis patients.

Detailed description

Part 1 will evaluate safety of APG-1252 monotherapy using a 3+3 dose escalation study design. The starting dose of APG-1252 monotherapy will be 160 mg administered as an intravenous injection over 30 minutes once weekly in a 28-day cycle. If the APG-1252 at 160 mg is tolerated (0/3 and ≤ 1/6 DLTs), dose escalation to 240 mg will be evaluated and declared as recommended phase 2 dose (RP2D) if tolerated. No doses higher than 240 mg once per week will be explored. If the 160 mg once weekly dose schedule is not tolerated (≥ 2/3 or ≥ 2/6 DLTs) de-escalation to 80 mg once weekly dose will be explored. No doses under 80 mg of APG-1252 will be explored as monotherapy. Maximum tolerated dose (MTD)/RP2D is defined as the highest dose with ≤ 1/6 patients with dose limiting toxicities. A maximum of 6 patients will be treated at the APG-1252 monotherapy dose level to further characterize safety. Part 2 will commence once APG-1252 monotherapy MTD/RP2D is determined following review of safety and tolerability of APG-1252 monotherapy and discussion between sponsor and investigators. In Part 2, APG-1252 will be tested in combination with ruxolitinib. Part 2 will evaluate tolerability and clinical benefit of the combination APG-1252 plus ruxolitinib using a 3+3 dose escalation design. Patients starting APG-1252 treatment as an addition to ruxolitinib should have been on ruxolitinib daily dose for at least 5 days at the same dose. If they were on fedratinib they should discontinue fedratinib and switch to ruxolitinib for at least 5 days before the addition of APG-1252. The starting dose of APG-1252 in Part 2, will be one dose level lower than the MTD of APG-1252 as monotherapy (i.e, at 80 mg if MTD is 160 and 160 mg if MTD is 240 mg) and will be increased to a maximum of 240 mg once per week, added to ruxolitinib. Once the MTD/RP2D of combination arm is determined, additional patients up to a maximum of 15 will be treated at the RP2D to further evaluate safety and clinical benefit.

Conditions

• Myelofibrosis

Interventions

Type	Name	Description
DRUG	APG-1252	infusion once weekly
DRUG	Ruxolitinib	taken orally twice a day

Timeline

• Start date: 2020-12-15
• Primary completion: 2022-12-15
• Completion: 2023-06-15
• First posted: 2020-04-21
• Last updated: 2022-07-12

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study