NCT05753501
Brief summary
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. Dose expansion part 2A will follow to further determine the safety and change in disease activity in participants with first line treatment (1L[non-US only]), second line or later of treatment (2L)+ CLL/SLL or third line or later of treatment (3L+) non-GCB DLBCL receiving ABBV-101 alone. Dose expansion Part 2B (non-US only) will follow to determine the safety and change in disease activity in participants with 1L or 2L+ CLL/SLL receiving ABBV-101 in combination with oral venetoclax. Approximately 390 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 100 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101 alone or oral ABBV-101 at a dose determined in the dose escalation phase in combination with oral venetoclax, as part of the approximately 100 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.
Interventional study
- 1
- 2
- 3
- 4
Age:
18 Years and older.
Inclusion Criteria:
- For Dose Escalation (Part 1) 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)
1. For Dose Escalation (Part 1) 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.
2. For Dose Escalation (Part 1) 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)
- For Dose Expansion (Part 2a) CLL/SLL only: Participants with a documented diagnosis
of CLL/SLL in their first-line or later treatment.
- For Dose Expansion (Part 2a) 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 documented diagnosis of CAR-T/HCT R/R or ineligible non-GCB
DLBCL who are in their third line or later treatment with histology based on
criteria established by the WHO.
- For Dose Exploration of ABBV-101 combination with venetoclax (Part 2b) CLL/SLL only:
Participants with a documented diagnosis of CLL/SLL in their first-line or later
treatment: In safety lead-in for each dose level, participants must have received at
least one prior systemic therapy.
- 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.
