A Study of AC676 for the Treatment of Relapsed/Refractory B-Cell Malignancies

Relapsed/Refractory B-cell Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05780034
• Other study ID #: AC676-001
• Status: Recruiting
• Phase: Phase 1
• Start date: June 20, 2023
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Accutar Biotechnology Inc
• Contact: Accutar Biotechnology
• Phone: 908-340-0879
• Email: medical[@]accutarbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Relapsed/Refractory B-cell Malignancies

Intervention

Drug:
• AC676
AC676 will be given orally (PO) on a 28-day cycle.

Locations

Country	Name	City	State
United States	The Ohio State University - The James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Tennessee Oncology	Nashville	Tennessee
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Accutar Biotechnology Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs) from AC676 monotherapy		From cycle 1 day 1 to Cycle 1 day 28. Cycles are 28 days.
Primary	Incidence of treatment-emergent adverse events (TEAEs) and clinically significant Grade 3 or higher laboratory abnormalities using CTCAE v5.0 criteria.		Approximately 18 months
Primary	Maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D)		Approximately 18 months
Secondary	Pharmacokinetic Analysis: area under the plasma concentration-time curve over the dosing interval (AUC(0-inf))		Up to approximately 20 weeks
Secondary	Pharmacokinetic Analysis: area under the plasma concentration-time curve from over the dosing interval (AUC(0-tau))		Up to approximately 20 weeks
Secondary	Pharmacokinetic Analysis: maximum plasma concentration (Cmax)		Up to approximately 20 weeks
Secondary	Pharmacokinetic Analysis: time to maximum plasma concentration (tmax)		Up to approximately 20 weeks
Secondary	Pharmacokinetic Analysis: terminal elimination half-life (t1/2)		Up to approximately 20 weeks
Secondary	Objective Response Rate (ORR) in patients receiving AC676		Approximately 18 months
Secondary	Duration of Response (DOR) in patients receiving AC676		Approximately 18 months
Secondary	Time to Response (TTR) in patients receiving AC676		Approximately 18 months
Secondary	Disease Control Rate (DCR) in patients receiving AC676		Approximately 18 months
Secondary	Progression Free Survival rate (PFS) in patients receiving AC676		Approximately 18 months