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

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.

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.