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

AbbVie

Status and phase: Enrolling; Phase 1

Conditions: Hematologic Cancer

Treatments: Drug: ABBV-101

Study type: Interventional

Funder types: Industry

Identifiers

NCT05753501

M23-647

2023-503594-38-00 (Other Identifier)

Details and patient eligibility

About

Non-Hodgkin's lymphoma (NHL) is a cancer that arises from the transformation of normal B and T lymphocytes (white blood cells). The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of ABBV-101 in adult participants in relapsed or refractory (R/R) non-Hodgkin's lymphomas: third line or later of treatment (3L) + chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large b-cell lymphoma (DLBCL), non-germinal center B cell (GCB) DLBCL, mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), or transformed indolent NHL. Adverse events will be assessed.

ABBV-101 is an investigational drug being developed for the treatment of NHL. This study will include a dose escalation phase to determine the maximum administered dose (MAD)/Maximum tolerated dose (MTD) of ABBV-101 and a dose expansion phase to determine the change in disease activity in participants with CLL or non-GCB DLBCL. Approximately 128 adult participants with multiple NHL subtypes will be enrolled in the study in sites world wide.

In the Dose Escalation phase of the study participants will receive escalating oral doses of ABBV-101, until the MAD/MTD is determined, as part of the approximately 60 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 60 month study duration .

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Enrollment: 128 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• For Dose Escalation (Part 1) only: Participants with documented diagnosis for one of the following 3L+ B-cell malignancies, from one of the following WHO-defined histologies (Swerdlow et al 2016):

  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • 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)

• For Dose Expansion (Part 2) only: Participants with documented diagnosis of CLL who are 3L+ including those with Bruton's tyrosine kinase (BTK) mutations or CAR-T/HCT R/R or ineligible non-GCB DLBCL who are 3L+ with histology based on criteria established by the World Health Organization (WHO).

• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.

• 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.

• Participants with prior central nervous system (CNS) disease that have been effectively treated may be eligible.

Exclusion criteria

• Previously treated with a Bruton's tyrosine kinase (BTK) degrader.
• Known active CNS disease, or primary CNS lymphoma.
• Uncontrolled active systemic infection, or active cytomegalovirus infection, known history of human immunodeficiency virus (HIV), active hepatitis B or C infection.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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128 participants in 3 patient groups

Dose Escalation ABBV-101

Experimental group

Description:

Participants with relapsed or refractory (R/R) Non-Hodgkin's lymphoma (NHL) will receive escalating doses of ABBV-101, until the maximum administered dose (MAD)/Maximum tolerated dose (MTD) is determined, as part of the approximately 60 month study duration.

Treatment:

Drug: ABBV-101

Dose Expansion ABBV-101 R/R Chronic Lymphocytic Lymphoma (CLL)

Experimental group

Description:

Participants with R/R CLL will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 60 month study duration.

Treatment:

Drug: ABBV-101

Dose Expansion ABBV-101 R/R non-GCB DLBCL

Experimental group

Description:

Participants with R/R non-germinal center B cell (GCB) diffuse large B-cell lymphoma (DLBCL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 60 month study duration.

Treatment:

Drug: ABBV-101