NCT04260022

Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL

A Phase Ib Study of the Pharmacokinetics, Safety and Efficacy of Orally Administered HQP1351 in Subjects With Refractory Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 242 (estimated)
• Sponsor: Ascentage Pharma Group Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A multi-center, open-label, randomized, phase Ib study to evaluate the pharmacokinetics (PK) of HQP1351 and to determine the recommended phase 2 dose (RP2D) of HQP1351 in subjects with CML chronic phase (CP), accelerated phase (AP), or blast phase (BP) or with Ph+ ALL, who have experienced resistance or intolerance to at least two tyrosine kinase inhibitors (TKIs) or in subjects with Ph+ B-cell precursor (BCP) ALL or lymphoid blast phase CML (CML LBP), who have experienced resistance or intolerance to at least one second or later generation TKI.

Detailed description

Approximately 40 patients will be randomized at 3:3:2 ratio into one of three HQP1351 monotherapy dose cohorts (Cohort A, B, and C): 30 mg every other day (QOD), 40 mg QOD, and 50 mg QOD, with 15, 15, and 10 patients in Cohort A, B, and C. The first cycle of 28 days is considered as the dose-limiting toxicity (DLT) observation period. If the incidence of DLTs exceeds 20% (2 patients) in 50 mg dose cohort during the first cycle of therapy, this dose cohort will be stopped. The randomization will be stratified to 4 groups: T315I mutated CML-CP and CML-AP, T315I un-mutated CML-CP, T315I unmutated CML-AP, and CML-BP and Ph+ ALL to ensure that the subgroups are represented across all dose cohorts. Blood samples will be collected from each subject at specified time points to evaluate the PK of HQP1351. RP2D of HQP1351 will be determined based on the comprehensive analyses of the PK, safety, and efficacy data of the US patients treated with HQP1351, when compared with that in the Chinese patients. Eligible patients will have disease resistance to or intolerance to at least two TKIs, for patients with T315I mutation, number of pretreated TKIs is not restricted. Patients will be administered HQP1351 orally QOD during a period of 28 days (1 cycle). Cohort D (HQP1351 + blinatumomab) will enroll patients with relapsed/refractory Ph+ BCP ALL or CML-BP using a dose escalation and expansion design. Patients will be administered HQP1351 orally QOD at an assigned dose with blinatumomab at repeated 42-day cycles. The first cycle of 42 days is considered as the DLT observation period. The initial dose of HQP1351 will be 30 mg QOD.

Conditions

• Leukemia, Myeloid, Chronic
• Myeloid Leukemia
• Chronic Myeloid Leukemia
• Philadelphia Positive Acute Lymphoblastic Leukemia
• B Cell Precursor Type Acute Leukemia

Interventions

Type	Name	Description
DRUG	Ascentage Pharma HQP1351 bioavailable inhibitor	HQP1351 taken by mouth every other day
DRUG	Blinatumomab	Administered in all patients as a continuous IV infusion at the dosage of 28μg daily (9μg daily for Cycle 1 Day 1 to Day 7).

Timeline

• Start date: 2020-01-09
• Primary completion: 2029-12-27
• Completion: 2030-03-31
• First posted: 2020-02-07
• Last updated: 2025-11-05

Locations

9 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study