Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets

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

B-cell malignancies are a group of cancers of B lymphocytes, a type of white blood cell responsible for fighting infections. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-525 as a monotherapy.

ABBV-525 is an investigational drug being developed for the treatment of B-Cell Malignancies. Study doctors put the participants in groups called treatment arms. Participants will receive ABBV-525 at different doses. Approximately 150 adult participants will be enrolled in the study across sites worldwide.

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.

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 Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-Cell Lymphoma; Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; B Cell Malignancies
• Intervention / Treatment: Drug: ABBV-525

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Bankstown, New South Wales, Australia, 2200
      • Bankstown-Lidcombe Hospital /ID# 260191
    • Orange, New South Wales, Australia, 2800
      • Orange Health Service /ID# 260473
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health - Monash Medical Centre /ID# 246366
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital /ID# 248592
• Belgium
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 246462
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 246461
• France
  • Nord
    • Lille, Nord, France, 59037
      • CHRU Lille - Hopital Claude Huriez /ID# 252054
  • Occitanie
    • Toulouse, Occitanie, France, 31059
      • IUCT Oncopole /ID# 259409
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin Campus Virchow-Klinikum /ID# 252062
• Israel
  • Central District
    • Beer Ya'akov, Central District, Israel, 70300
      • Shamir Medical Center /ID# 257711
    • Petah Tikva, Central District, Israel, 4941492
      • Rabin Medical Center. /ID# 257665
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 251441
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 251442
• South Korea
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Seoul National University Hospital /ID# 266340
    • Seoul, Seoul Teugbyeolsi, South Korea, 05505
      • Asan Medical Center /ID# 266341
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center /ID# 266415
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 246543
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall de Hebron /ID# 245475
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal /ID# 246540
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 246538
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 246537
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital /ID# 266414
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital /ID# 266343
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust /ID# 250324
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital /ID# 250325
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Leeds Teaching Hospitals NHS Trust /ID# 245470
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles Medical Center /ID# 246357
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine /ID# 259081
  • Florida
    • Miami Beach, Florida, United States, 33140-2948
      • Mount Sinai Medical Center-Miami Beach /ID# 248251
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology, Inc /ID# 250113
    • Indianapolis, Indiana, United States, 46202-5116
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center /ID# 259872
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center Clinic /ID# 249586
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest /ID# 252359
  • New York
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 245459
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health Levine Cancer Institute /ID# 246363
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University Of Cincinnati Medical Center /ID# 262288
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 245463
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Hospital /ID# 259924
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties - Tacoma /ID# 260376

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Dose 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABBV-525 Dose Escalation; Participants will receive escalating doses of ABBV-525 until doses for optimization are determined, as part of an approximately 64 month study period.	Drug: ABBV-525; Oral; Tablet
Experimental: ABBV-525 Dose Optimization; Participants will receive one of two doses of ABBV-525 until the recommended phase 2 dose (RP2D) is determined, as part of an approximately 64 month study period.	Drug: ABBV-525; Oral; Tablet
Experimental: ABBV-525 Dose Expansion; Participants will receive the RP2D dose of ABBV-525, as part of an approximately 64 month study period.	Drug: ABBV-525; Oral; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AE)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is defined as any untoward medical occurrence, whether associated with study drug or not, that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event requiring medical or surgical intervention to prevent serious outcome.	Up to Approximately 64 Months
Number of Participants With Dose-Limiting Toxicities (DLT)	A DLT is defined as any AE for which a clear alternative cause cannot be established (eg, attributed to the disease under study, another disease, or to a concomitant medication by the study investigators or medical monitor).	Up to Approximately 28 Days
Number of Tumor Lysis Syndrome (TLS)	TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.	Up to Approximately 64 Months
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters	Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator will assess the results for clinical significance.	Up to Approximately 64 Months
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters	Vital sign parameters included body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate. The investigator will assess the results for clinical significance.	Up to Approximately 64 Months
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)	A standard 12-lead ECG will be performed. The investigator will assess the results for clinical significance.	Up to Approximately 64 Months
Maximum Observed Plasma Concentration (Cmax) of ABBV-525	Maximum observed plasma concentration of ABBV-525.	Up to 12 Months
Time to Cmax (Tmax) of ABBV-525	Time to Cmax of ABBV-525.	Up to 12 Months
Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525	Area under the plasma concentration-time curve of ABBV-525.	Up to 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR)/very good partial response (VGPR)/partial response (PR) in participants receiving at least 1 dose of study drug.	Up to Approximately 64 Months
Duration of Response (DOR)	DOR is defined for participants achieving CR/VGPR/PR as the time from the initial response per Investigator review to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately 64 Months

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; B-cell Malignancies; ABBV-525
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasms; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: M23-324; 2022-503136-13 (Other Identifier: EU CT); 2022-503136-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No