Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies

Prior treatment

• Previously treated with a Bruton's tyrosine kinase (BTK) degrader, except ABBV-101.
• Known active central nervous system (CNS) disease, or primary CNS lymphoma. Participants with prior CNS disease that have been effectively treated may be eligible.
• Uncontrolled active systemic infection requiring systemic treatment that is ongoing or was completed \<= 14 days before the first dose of study drug, or active cytomegalovirus infection.

• For Dose Escalation only (including backfill): Participants have received at least two prior systemic therapies, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), have measurable disease requiring treatment, and have a documented diagnosis for one of the following third line or later B-cell malignancies, from one of the following world health organization (WHO)-defined histologies (Swerdlow et al 2016):
  • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
  • For Dose Escalation backfill only - Bruton's tyrosine kinase inhibitor (BTKi)/Bruton's tyrosine kinase degrader (BTKd)-naïve CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received at least one prior systemic therapy that cannot be a BTK inhibitor or degrader, and, with the exception of BTK pathway agents, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment.
  • For Dose Escalation backfill only - BTKi/BCL-2i combination regimen-exposed 2L CLL/SLL. Participants with a documented diagnosis of CLL/SLL who have received one prior systemic therapy with a BTKi and BCL-2i combination regimen, have no available therapies known to provide clinical benefit (e.g., standard chemotherapy or HCT), and have measurable disease requiring treatment.
  • Chimeric antigen receptor T-cells (CAR-T)/hematopoietic cell transplant (HCT) relapsed/refractory (R/R) or ineligible diffuse large b-cell lymphoma (DLBCL) from the following histologies: DLBCL not otherwise specified (NOS) (germinal center B cell \[GCB\] and non-GCB DLBCL), T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS.
  • Mantle cell lymphoma (MCL)
  • Follicular lymphoma \[FL\] (grades 1-3b)
  • Marginal zone lymphoma \[MZL\] (splenic, extranodal, and nodal)
  • Waldenström macroglobulinemia (WM)
  • Transformed indolent non-Hodgkin's lymphoma (iNHL)
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2. For EU only: Participant has an ECOG PS of 0 or 1.
• Participant has a life expectancy \>= 12 weeks.
• Prior Bruton's tyrosine kinase inhibitor (BTKi) is allowed.
• Adequate hematologic, renal, and hepatic function per the protocol.