Clinical trial NCT05780034: A Study of AC676 for the Treatment of Relapsed/Refractory B-Cell Malignancies
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory B-cell Malignancies
Keywords: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Mantle Cell Lymphoma (MCL)
Follicular Lymphoma (FL)
Non-Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL)
Marginal Zone Lymphoma (MZL
Waldenström Macroglobulinemia (WM)
Non-Hodgkin Lymphoma (NHL)
Bruton's tyrosine kinase-BTK
BTK Degrader
AC676
AC0676
Lead sponsor: Accutar Biotechnology Inc
Sponsor class: INDUSTRY
First posted: 2023-03-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) from AC676 monotherapy
timeFrame: From cycle 1 day 1 to Cycle 1 day 28. Cycles are 28 days.
measure: Incidence of treatment-emergent adverse events (TEAEs) and clinically significant Grade 3 or higher laboratory abnormalities using CTCAE v5.0 criteria.
timeFrame: Approximately 18 months
measure: Maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D)
timeFrame: Approximately 18 months
Secondary outcomes:
measure: Pharmacokinetic Analysis: area under the plasma concentration-time curve over the dosing interval (AUC(0-inf))
timeFrame: Up to approximately 20 weeks
measure: Pharmacokinetic Analysis: area under the plasma concentration-time curve from over the dosing interval (AUC(0-tau))
timeFrame: Up to approximately 20 weeks
measure: Pharmacokinetic Analysis: maximum plasma concentration (Cmax)
timeFrame: Up to approximately 20 weeks
measure: Pharmacokinetic Analysis: time to maximum plasma concentration (tmax)
timeFrame: Up to approximately 20 weeks
measure: Pharmacokinetic Analysis: terminal elimination half-life (t1/2)
timeFrame: Up to approximately 20 weeks
measure: Objective Response Rate (ORR) in patients receiving AC676
timeFrame: Approximately 18 months
measure: Duration of Response (DOR) in patients receiving AC676
timeFrame: Approximately 18 months
measure: Time to Response (TTR) in patients receiving AC676
timeFrame: Approximately 18 months
measure: Disease Control Rate (DCR) in patients receiving AC676
timeFrame: Approximately 18 months
measure: Progression Free Survival rate (PFS) in patients receiving AC676
timeFrame: Approximately 18 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Columbus
country: United States
facility: The Ohio State University - The James Cancer Hospital and Solove Research Institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
References: