A Phase I Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Malignancy Activity of AC676 in Patients With Relapsed/Refractory B-cell Malignancies
Summary
This clinical trial is evaluating a drug called AC676 in participants with Relapsed/Refractory B-cell Malignancies. The main goals of the study are to: * Identify the recommended dose of AC676 that can be given safely to participants * Evaluate the safety profile of AC676 * Evaluate the pharmacokinetics of AC676 * Evaluate the effectiveness of AC676
Detailed description
AC676-001 is a Phase I, first-in-human, open-label, multi-center dose-escalation study of AC676 given as a single agent. AC676 is an investigational medicinal product that is an orally bioavailable BTK degrader for the treatment of B-cell malignancies.
Arms & interventions
- DrugAC676
AC676 will be given orally (PO) on a 28-day cycle.
Outcome measures
Primary
Incidence of dose limiting toxicities (DLTs) from AC676 monotherapy
Time frame: From cycle 1 day 1 to Cycle 1 day 28. Cycles are 28 days.
Incidence of treatment-emergent adverse events (TEAEs) and clinically significant Grade 3 or higher laboratory abnormalities using CTCAE v5.0 criteria.
Time frame: Approximately 18 months
Maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D)
Time frame: Approximately 18 months
Secondary
Pharmacokinetic Analysis: area under the plasma concentration-time curve over the dosing interval (AUC(0-inf))
Time frame: Up to approximately 20 weeks
Pharmacokinetic Analysis: area under the plasma concentration-time curve from over the dosing interval (AUC(0-tau))
Time frame: Up to approximately 20 weeks
Pharmacokinetic Analysis: maximum plasma concentration (Cmax)
Time frame: Up to approximately 20 weeks
Pharmacokinetic Analysis: time to maximum plasma concentration (tmax)
Time frame: Up to approximately 20 weeks
Pharmacokinetic Analysis: terminal elimination half-life (t1/2)
Time frame: Up to approximately 20 weeks
Objective Response Rate (ORR) in patients receiving AC676
Time frame: Approximately 18 months
Duration of Response (DOR) in patients receiving AC676
Time frame: Approximately 18 months
Time to Response (TTR) in patients receiving AC676
Time frame: Approximately 18 months
Disease Control Rate (DCR) in patients receiving AC676
Time frame: Approximately 18 months
Progression Free Survival rate (PFS) in patients receiving AC676
Time frame: Approximately 18 months
Eligibility criteria
Study locations (9)
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Florida Cancer Specialists
Sarasota, Florida, 34232
University of North Carolina
Chapel Hill, North Carolina, 27599
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
The Ohio State University - The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
Oregon Health & Science University
Portland, Oregon, 97239
Tennessee Oncology
Nashville, Tennessee, 37302
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Swedish Cancer Institute
Seattle, Washington, 98104