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

Sponsor

Accutar Biotechnology Inc (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05780034

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory B-cell Malignancies	Drug: AC676	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AC676 Dose Escalation Participants will receive an assigned dose of AC676 in a 28-days cycle.	Drug: AC676 AC676 will be given orally (PO) on a 28-day cycle.

Arm

Intervention/Treatment

Experimental: AC676 Dose Escalation

Participants will receive an assigned dose of AC676 in a 28-days cycle.

Drug: AC676

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

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) from AC676 monotherapy [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. [Approximately 18 months]
Maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) [Approximately 18 months]

Secondary Outcome Measures

Pharmacokinetic Analysis: area under the plasma concentration-time curve over the dosing interval (AUC(0-inf)) [Up to approximately 20 weeks]
Pharmacokinetic Analysis: area under the plasma concentration-time curve from over the dosing interval (AUC(0-tau)) [Up to approximately 20 weeks]
Pharmacokinetic Analysis: maximum plasma concentration (Cmax) [Up to approximately 20 weeks]
Pharmacokinetic Analysis: time to maximum plasma concentration (tmax) [Up to approximately 20 weeks]
Pharmacokinetic Analysis: terminal elimination half-life (t1/2) [Up to approximately 20 weeks]
Objective Response Rate (ORR) in patients receiving AC676 [Approximately 18 months]
Duration of Response (DOR) in patients receiving AC676 [Approximately 18 months]
Time to Response (TTR) in patients receiving AC676 [Approximately 18 months]
Disease Control Rate (DCR) in patients receiving AC676 [Approximately 18 months]
Progression Free Survival rate (PFS) in patients receiving AC676 [Approximately 18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult male and female patients, at least 18 years-of-age at the time of signature of the informed consent form (ICF).
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).
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:

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. Any patient who experienced graft versus host disease during a prior allogenic stem cell transplant will not be allowed on study.

History of central nervous system lymphoma/leukemia in remission for less than 2 years.
Medical history of active bleeding within 2 months prior to study entry, or susceptible to bleeding by the judgement of investigator.