A First-in-Human Study of ABBV-525 (MALT1 Inhibitor) in B-Cell Malignancies

Study Identifier:
M23-324
CT.gov Identifier:
NCT05618028
EudraCT Identifier:
202250000000
EU Trial (CTIS) Number:
2022-503136-13-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

To assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-525 as a monotherapy in patients with B-Cell Malignancies.

Part 1 aims to establish the maximum administered dose/maximum tolerated dose of ABBV-525 and is primarily guided by a Bayesian optimal interval design. Part 2 aims to identify the RP2D of ABBV-525. Part 3 will further characterize the safety profile of ABBV-525 at the RP2D.

Safety assessments include dose-limiting toxicities, adverse events (per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0), clinical laboratory parameters, vital signs, and electrocardiogram variables. PK parameters, including maximum observed plasma concentration (Cmax), time to Cmax, and area under the concentration-time curve will be analyzed using noncompartmental methods. Efficacy will be assessed through response per disease-specific criteria (including International Workshop on Chronic Lymphocytic Leukemia, International Workshop on Waldenstrom’s Macroglobulinemia, and Lugano classification). Duration of response will be evaluated by Kaplan-Meier estimates. Biomarker data will be analyzed as change from baseline and summarized for each scheduled postbaseline visit.

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.
  • Lymphoma
  • Leukemia
  • 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: ABBV-525 Dose Escalation
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  • Drug: Experimental: ABBV-525 Dose Optimization
  • Drug: Experimental: ABBV-525 Dose Expansion
  • Drug: Intervention/treatment:
  • Drug: In part 1 (dose escalation), participants will receive escalating oral doses of ABBV-525. In part 2 (dose optimization), participants will receive one of two oral doses of ABBV-525, until the recommended phase 2 dose (RP2D) is determined. In part 3 (dose expansion), participants will receive the RP2D oral dose of ABBV-525. The estimated duration of the study is up to 64 months.
  • Drug: 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 a hospital or clinic and may require frequent medical assessments, blood tests, and scans.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • ose Escalation (Part 1) Only: Participants with a documented diagnosis of one of the following third line or later of treatment (3L)+ mature B-cell malignancies, from the World Health Organization (WHO)-defined histologies as defined in the protocol.
    • Dose Optimization (Part 2) Only: Participants with documented diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with histology based on WHO criteria, with measurable disease requiring treatment as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL).
    • Dose Expansion (Part 3) Only: Participants with documented diagnosis of one of the 3L+ mature B-cell malignancies based on WHO criteria listed in the protocol, with measurable disease requiring treatment.
    • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
    • Participant has a life expectancy >= 12 weeks.
    • Adequate hematological and hepatic function as defined in the protocol.
    • Must have archival or freshly collected tumor tissue for correlative studies before study enrollment.
    • Participants with prior central nervous system (CNS) disease that has been effectively treated may be eligible.
    • Participants with resolved coronavirus disease 2019 (COVID-19) infection are eligible..
    Exclusion criteria
    • Known active CNS disease, or primary CNS lymphoma.
    • Known bleeding disorders.
    • Known history of stroke or intracranial hemorrhage within 12 months prior to first dose of study treatment.
    • Uncontrolled active systemic infection, or active cytomegalovirus infection.
    • Active and/or chronic hepatitis B or C infection and/or the criteria listed in the protocol.
    • Known history of human immunodeficiency virus (HIV).
    • Known active COVID-19 infection. Participant must not have signs/symptoms associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 infection during screening. If participant has signs/symptoms suggestive of COVID-19 infection, the participant must have a negative molecular (e.g., polymerase chain reaction) test or 3 negative antigen test results at least 24 hours apart.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Andrew Sochacki
    Status
    Recruiting
    Condition(s) Treated at Site
    Lymphoma
    Leukemia
    Hematological Cancer