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: 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 first line treatment (1L), second line or later of treatment (2L)+ CLL/SLL or third line or later of treatment (3L) non-GCB DLBCL. Approximately 340 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 88 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 88 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: 340 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• For Dose Escalation (Part 1) only: 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)

  • 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)

    1. For Dose Escalation (Part 1) - BTKi/BTKd-naïve CLL/SLL backfill only: 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.
    2. For Dose Escalation (Part 1) - BTKi/BTKd-naïve CLL/SLL backfill only: 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.

• For Dose Expansion (Part 2) CLL/SLL only: Participants with a documented diagnosis of CLL/SLL who have received at least one prior systemic therapy.

• For Dose Expansion (Part 2) DLBCL only: 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 of CAR-T/HCT R/R or ineligible non-GCB DLBCL in their third line or later treatment 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. 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.

Exclusion criteria

• Previously treated with a Bruton's tyrosine kinase (BTK) degrader.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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340 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 88 month study duration.

Treatment:

Drug: ABBV-101

Dose Expansion ABBV-101 R/R CLL/SLL

Experimental group

Description:

Participants with R/R chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 88 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 88 month study duration.

Treatment:

Drug: ABBV-101