Safety, Tolerability and Pharmacokinetics Study of KPG-818 in Hematological Malignancies Subjects

Summary

Participation Requirements

Description

This is a Phase 1, multicenter, open-label, multiple-ascending dose study to evaluate the safety, PK, and preliminary clinical activity of KPG-818 as a single agent in adult subjects with selected hematological malignancies. The study center(s) will be in the US. After providing informed consent, su...

This is a Phase 1, multicenter, open-label, multiple-ascending dose study to evaluate the safety, PK, and preliminary clinical activity of KPG-818 as a single agent in adult subjects with selected hematological malignancies. The study center(s) will be in the US. After providing informed consent, subjects will be assessed for study eligibility at the Screening visit (Days -28 to -1). Cohorts of 3 to 6 subjects per dose level will be given escalating doses of KPG-818 during Days 1 to 21 of each 28-day cycle orally until progressive disease (PD), unacceptable toxicity, the subject withdraws, or any other study withdrawal criterion is met. The 4 planned dose escalation cohorts will be 5, 10, 20, and 30 mg followed by dose expansion. The dose of KPG-818 for the first cohort will be 2 mg/day. Dose escalation will use an accelerated titration design (ATD) where the first two dose levels will include one subject each. Subsequent dose levels will use a 3+3 approach to establish a MTD. The first subject will receive the initial escalation dose level 5 mg/day and be dosed on Day 1 to 21 over a 28-day treatment cycle, and in the absence of a DLT or Grade 2 or greater study drug-related AE and after review of the data from the first full cycle by the Safety Review Committee (SRC), the next subject will receive 10 mg/day followed by review of the data by the SRC. Once 20 mg/day is reached, the enrolment will revert to a standard 3+3 escalation design. If 1 or more Grade 2 or greater study drug-related AE is observed at dose levels 5 or 10 mg/day, two additional subjects will be enrolled at the same dose level, and dose escalation reverts to a standard 3+3 escalation design. If 1 or more DLT is observed at dose levels of 5 or 10 mg/day, five additional subjects will be enrolled at the same dose level and dose escalation reverts to a standard 3+3 escalation design (Table 3). Enrolment to 20 mg/day will follow a standard 3+3 escalation design. The highest dose level which may be tested is 30 mg KPG-818. Dose escalation will follow a 3+3 design and dose-limiting toxicity (DLT) will be assessed during the 28-day DLT evaluation period. The Safety Monitoring Committee (SMC) will be responsible for dose escalation decisions, including whether to modify the dose escalation based on the DLT observations or determine RP2D. Escalation to the Maximal Tolerated Dose (MTD) is not appropriate if activity plateaus at a lower dose.

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