First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants With B-cell Malignancies

Study Identifier:
M23-647
CT.gov Identifier:
NCT05753501
EudraCT Identifier:
202350000000
EU Trial (CTIS) Number:
2023-503594-38-00
Study Contact Information:
N/A
Recruitment Complete

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Study 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: 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 in 28-day cycles, until the MAD/MTD is determined. In the dose expansion phase of the study participants receive oral ABBV-101 in 28-day cycles.

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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Hematological Cancer
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Dose Escalation ABBV-101
    • Read More
  • Drug: Drug: ABBV-101
  • Drug: ASCO 2024
  • Drug: ..ABBV-101 is administered orally until disease progression, intolerable toxicity, or other study discontinuation criteria are met. Safety assessments include, but are not limited to, AEs, clinical laboratory parameters, vital signs, and ECG. Response evaluations are performed per disease-specific response criteria at screening and every 8 weeks (1st year), 3 months (2nd year), or 4 months (3rd year onward) until progressive disease.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Daniel Morillo Giles
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Hematological Cancer
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Agustin Penedo
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Hematological Cancer