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

• ClinicalTrials.gov Identifier: NCT05618028
• Recruitment Status: Recruiting
• First Posted: November 16, 2022
• Last Update Posted: April 19, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: November 14, 2022
• First Posted Date: November 16, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: April 4, 2023
• Estimated Primary Completion Date: June 27, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2023)

• Number of Participants With Adverse Events (AE) [ Time Frame: Up to Approximately 64 Months ]
  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.
• Number of Participants With Dose-Limiting Toxicities (DLT) [ Time Frame: Up to Approximately 28 Days ]
  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).
• Number of Tumor Lysis Syndrome (TLS) [ Time Frame: Up to Approximately 64 Months ]
  TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.
• Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Approximately 64 Months ]
  Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator will assess the results for clinical significance.
• Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters [ Time Frame: Up to Approximately 64 Months ]
  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.
• Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) [ Time Frame: Up to Approximately 64 Months ]
  A standard 12-lead ECG will be performed. The investigator will assess the results for clinical significance.
• Maximum Observed Plasma Concentration (Cmax) of ABBV-525 [ Time Frame: Up to 12 Months ]
  Maximum observed plasma concentration of ABBV-525.
• Time to Cmax (Tmax) of ABBV-525 [ Time Frame: Up to 12 Months ]
  Time to Cmax of ABBV-525.
• Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525 [ Time Frame: Up to 12 Months ]
  Area under the plasma concentration-time curve of ABBV-525.

Original Primary Outcome Measures (submitted: November 14, 2022)

• Number of Participants With Adverse Events (AE) [ Time Frame: Up to Approximately 64 Months ]
  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.
• Number of Participants With Dose-Limiting Toxicities (DLT) [ Time Frame: Up to Approximately 28 Days ]
  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).
• Number of Tumor Lysis Syndrome (TLS) [ Time Frame: Up to Approximately 64 Months ]
  TLS is confirmed by evaluation of electrolyte and fluid status and renal status including urine output.
• Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Approximately 64 Months ]
  Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator will assess the results for clinical significance.
• Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters [ Time Frame: Up to Approximately 64 Months ]
  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.
• Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) [ Time Frame: Up to Approximately 64 Months ]
  A standard 12-lead ECG will be performed. The investigator will assess the results for clinical significance.
• Maximum Observed Plasma Concentration (Cmax) of ABBV-525 [ Time Frame: Up to Approximately 64 Months ]
  Maximum observed plasma concentration of ABBV-525.
• Time to Cmax (Tmax) of ABBV-525 [ Time Frame: Up to Approximately 64 Months ]
  Time to Cmax of ABBV-525.
• Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-525 [ Time Frame: Up to Approximately 64 Months ]
  Area under the plasma concentration-time curve of ABBV-525.

Current Secondary Outcome Measures (submitted: November 14, 2022)

• Overall Response Rate (ORR) [ Time Frame: Up to Approximately 64 Months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to Approximately 64 Months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Diffuse Large B-Cell Lymphoma
• Chronic Lymphocytic Leukemia
• B Cell Malignancies
• Non-Hodgkin's Lymphoma

Intervention

Drug: ABBV-525

Oral; Tablet

Study Arms

• 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.
  Intervention: Drug: ABBV-525
• 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.
  Intervention: Drug: ABBV-525
• Experimental: ABBV-525 Dose Expansion
  Participants will receive the RP2D dose of ABBV-525, as part of an approximately 64 month study period.
  Intervention: Drug: ABBV-525

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2022): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 27, 2027
• Estimated Primary Completion Date: June 27, 2027 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Belgium, France, Israel, Spain, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT05618028
• Other Study ID Numbers: M23-324
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: April 2024