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RecruitingInterventionalPhase 1

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

NCT ID: NCT05780034Sponsor: Accutar Biotechnology IncLast updated: 2025-10-02

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1. Adult male and female patients, at least 18 years-of-age at the time of signature of the informed consent form (ICF). 2. Patients with histologically confirmed relapsed/refractory Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), non-GCB Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), or Waldenström Macroglobulinemia (WM). 3. Must have received at least 2 prior systemic therapies or have no other therapies to provide significant clinical benefit in the opinion of the Investigator or who are not amenable (intolerability, patient choice) to standard therapies. Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: 1. Treatment with any of the following: * Small molecule anti-cancer drugs within 5 half-lives or 2 days (whichever is longer, not to exceed 14 days). * Systemic chemotherapy within 14 days. * Radiation therapy within 14 days * Biologics (Antibodies) treatment within 28 days, * Radioimmunoconjugates or toxin conjugates within 12 weeks. * Prior Chimeric antigen receptor (CAR) T cell therapy (and prior use of immunoglobulin replacement therapy to treat associated adverse events) within 3 months. For patients with DLBCL, no prior CAR- T therapy is allowed. * Autologous or allogenic stem cell transplant within 100 days and must not have ongoing graft-versus-host disease (GVHD) and no ongoing therapy to treat GVHD. 2. History of central nervous system lymphoma/leukemia in remission for less than 2 years. 3. Medical history of active bleeding within 2 months prior to study entry, or susceptible to bleeding by the judgement of investigator.

Study locations (9)

Colorado Blood Cancer Institute

Denver, Colorado, 80218

Recruiting

Florida Cancer Specialists

Sarasota, Florida, 34232

Recruiting

University of North Carolina

Chapel Hill, North Carolina, 27599

Recruiting

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting

The Ohio State University - The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210

Recruiting

Oregon Health & Science University

Portland, Oregon, 97239

Recruiting

Tennessee Oncology

Nashville, Tennessee, 37302

Withdrawn

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

Recruiting

Swedish Cancer Institute

Seattle, Washington, 98104

Recruiting