A Phase I, Multicenter, Open-Label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-168 in Subjects With Relapsed or Refractory B-cell Malignancies.
Summary
This is a phase I, multi-center, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and clinical activity of LP-168 in subjects with relapsed or refractory B-cell malignancies. LP-168 is a small molecule inhibitor.
Detailed description
The primary objectives for the study are to assess the safety and tolerability profile, determine the maximum tolerated dose (MTD), and/or the recommended Phase 2 dose (RP2D) of LP-168 administered once or twice daily as a single agent dosed orally in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL); and to characterize the pharmacokinetics (PK) profile of LP-168 in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL). Secondary objectives of the study are to evaluate preliminary efficacy regarding the effect of LP-168 on progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL). Once the MTD is declared and the RP2D is established, additional subjects will be enrolled in a cohort expansion phase (Phase 1b).
Arms & interventions
- DrugLP-168
For the dose escalation phase, LP-168 will be given once or twice daily at the following dose levels:100 mg QD,150 mg QD, 100 mg BID, 300 mg QD, 150 mg BID, 450 mg QD, 225 mg BID, 600 mg QD, 800 mg QD, and 1000 mg QD.
- DrugLP-168
For the dose expansion phase, subjects will receive once or twice daily dose of LP-168 at the Recommended Phase 2 Dose (RP2D). The RP2D may be as high as the MTD and will be determined following evaluation of Phase I Dose Escalation results.
Outcome measures
Primary
Maximum Tolerated Dose (MTD)
When more than 1 DLT occurs in ≤ 6 subjects in a dosing cohort, dose escalation will be stopped and this dose level will be identified as the non-tolerated dose. Doses between the non-tolerated dose and the preceding lower dose, where ≤ 1 DLT occurred, may be explored to more precisely define the MTD.
Time frame: Up to 24 months, each cycle is 28 days
Recommended Phase 2 dose (RP2D)
The RP2D may be as high as the MTD or a lower dose and will be selected in discussion with the Investigators and the Sponsor based on longer term safety data, preliminary efficacy data, and PK data.
Time frame: Up to 24 months, each cycle is 28 days
Pharmacokinetic (PK) profile of LP-168
Maximum Plasma Concentration \[Cmax\]
Time frame: At Cycle 1: Day 1, Day 2, Day 8, Day 9, Day 15, Day 22, Day 28; At Cycle 3: Day 28; At Cycle 6 Day 28; (each cycle is 28 days)
Pharmacokinetic (PK) profile of LP-168
Area Under the Curve \[AUC\]
Time frame: At Cycle 1: Day 1, Day 2, Day 8, Day 9, Day 15, Day 22, Day 28; At Cycle 3: Day 28; At Cycle 6 Day 28; (each cycle is 28 days
Pharmacokinetic (PK) profile of LP-168
Time at Maximum Concentration \[Tmax\]
Time frame: At Cycle 1: Day 1, Day 2, Day 8, Day 9, Day 15, Day 22, Day 28; At Cycle 3: Day 28; At Cycle 6 Day 28; (each cycle is 28 days
Secondary
Progression-Free Survival (PFS)
Time frame: Up to 24 months, each cycle is 28 days
Objective Response Rate (ORR)
Time frame: Up to 24 months, each cycle is 28 days
Duration of Response (DOR)
Time frame: Up to 24 months, each cycle is 28 days
Eligibility criteria
Study locations (4)
Duke Univerisity
Durham, North Carolina, 27708
University of Cincinnati
Cincinnati, Ohio, 45221
Ohio State University
Columbus, Ohio, 43210
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112