A Phase 1, First-In-Human, Dose-Seeking Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Orally Administered MPT0E028 in Subjects With Advanced Solid Malignancies Without Standard Treatment
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Taipei Medical University
- Enrollment
- 23
- Locations
- 2
- Primary Endpoint
- the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of daily oral MPT0E028 in subjects with advanced solid malignancies
Overview
Brief Summary
The Dose Escalation Phase will determine the MTD of MPT0E028 and evaluate its safety and tolerability, PK, PD, and preliminary clinical effects; the subsequent Dose Confirmation Phase will be a cohort expansion at or below the MTD (i.e., an RP2D) of MPT0E028.
Detailed Description
This is an open-label, non-randomized, dose-escalation study that will evaluate MPT0E028 in subjects with advanced solid malignancies. Subjects will be treated with oral doses of MPT0E028 in consecutive, 28-day cycles, and will be evaluated regularly for safety. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive MPT0E028 at the discretion of the principal Investigator for up to 6 cycles. The Sponsor will keep providing drug for extension cycles to subjects whose disease is controlled at the end of 6th cycle until the end of the study or until the early study termination determined by sponsor. Subjects will return for a follow-up visit 28 days after completion of the end of Study.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 1
Subjects will be treated with oral doses of MPT0E028 in consecutive, 28-day cycles, and will be evaluated regularly for safety. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive MPT0E028 at the discretion of the principal Investigator for up to 6 cycles.
Intervention: MPT0E028 (Drug)
Outcomes
Primary Outcomes
the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of daily oral MPT0E028 in subjects with advanced solid malignancies
Time Frame: 28 days (Cycle 1)
Toxicity will be graded and recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events - (CTCAE v4.0). The MTD of MPT0E028 is defined as the highest dose level at which less than 1/3 of subjects experience DLT during Cycle 1 and have 6 subjects in total to confirm the safety of MTD.
the pharmacodynamic (PD) effects of MPT0E028 in subjects with advanced solid malignancies through the measurement of the biomarker peripheral blood mononuclear cell (PBMC) histone acetylation
Time Frame: baseline; Day 1, 15 of cycle1; Day 1 of Cycle 2, 3 and 4 (each cycle is 28 days)
PBMC histone acetylation status will be assessed.
the pharmacokinetic (PK) profile of MPT0E028 in subjects with advanced solid malignancies
Time Frame: baseline; Day 1, 8, 15 of Cycle1; Day 1 and 15 of Cycle 2, 3 and 4 (each cycle is 28 days)
PK parameters, including area under the curve, maximum plasma concentration, trough plasma concentration, time to maximum plasma concentration, apparent oral clearance, and plasma half-life will be determined.
Secondary Outcomes
No secondary outcomes reported