Clinical trial NCT05618028: Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets
Official title: A First-in-Human Study of ABBV-525 (MALT1 Inhibitor) in B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Diffuse Large B-Cell Lymphoma
Chronic Lymphocytic Leukemia
B Cell Malignancies
Non-Hodgkin's Lymphoma
Keywords: Diffuse Large B-Cell Lymphoma
B-cell Malignancies
Chronic Lymphocytic Leukemia
Non-Hodgkin's Lymphoma
ABBV-525
Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-11-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 100 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.


Eligibility criteria: 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) who are 3L+, +/- cysteine-to-serine point mutation at residue 481 of BTK-domain active site (C481S 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 non-germinal center B cell (GCB) Diffuse large B-cell lymphoma (DLBCL) who are 3L+ chimeric antigen receptor T-cells (CAR-T)/Hematopoietic cell transplant (HCT) relapsed/refractory (R/R) and/or ineligible with histology based on WHO criteria, with measurable disease requiring treatment.
* Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
* 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 hepatitis B or C infection.
* 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 (eg, polymerase chain reaction) test or 3 negative antigen test results at least 24 hours apart.

Primary outcomes:
measure: Number of Participants With Adverse Events (AE)
timeFrame: Up to Approximately 64 Months
measure: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: Up to Approximately 28 Days
measure: Number of Tumor Lysis Syndrome (TLS)
timeFrame: Up to Approximately 64 Months
measure: Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
timeFrame: Up to Approximately 64 Months
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters
timeFrame: Up to Approximately 64 Months
measure: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
timeFrame: Up to Approximately 64 Months
measure: Maximum Observed Plasma Concentration (Cmax) of ABBV-525
timeFrame: Up to 12 Months
measure: Time to Cmax (Tmax) of ABBV-525
timeFrame: Up to 12 Months
measure: Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525
timeFrame: Up to 12 Months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to Approximately 64 Months
measure: Duration of Response (DOR)
timeFrame: Up to Approximately 64 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles /ID# 246357
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 259081
state: Connecticut
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center-Miami Beach /ID# 248251
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc /ID# 250113
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center /ID# 259872
state: Indiana
city: New Orleans
country: United States
facility: Tulane Cancer Center Clinic /ID# 249586
state: Louisiana
city: Grand Rapids
country: United States
facility: START Midwest /ID# 252359
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 245459
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute /ID# 246363
state: North Carolina
city: Cincinnati
country: United States
facility: University Of Cincinnati Medical Center /ID# 262288
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 245463
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Hospital /ID# 259924
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties - Tacoma /ID# 260376
state: Washington
city: Clayton
country: Australia
facility: Monash University /ID# 246366
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital /ID# 248592
state: Victoria
city: Gent
country: Belgium
facility: UZ Gent /ID# 246462
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven /ID# 246461
state: Vlaams-Brabant
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 252054
state: Nord
city: Toulouse Cedex 9
country: France
facility: IUCT Oncopole /ID# 259409
state: Occitanie
city: Berlin
country: Germany
facility: Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 252062
city: Beer Ya'akov
country: Israel
facility: Shamir Medical Center /ID# 257711
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 251442
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 251441
state: Yerushalayim
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 257665
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 246537
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 245475
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 246543
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 246540
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 246538
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust /ID# 245470
state: West Yorkshire
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust /ID# 250324
city: Manchester
country: United Kingdom
facility: The Christie Hospital /ID# 250325
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: