Clinical trial NCT04804254: Study to Evaluate Adverse Events, Change in Disease Activity, Movement of Oral ABBV-623 and ABBV-992 Tablets in the Body of Adult Participants With B-cell Cancers
Official title: A Phase 1 First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of ABBV-623 and ABBV-992 in Subjects With B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: B-cell Lymphoma
Keywords: ABBV-623
ABBV-992
B-cell lymphoma
Cancer
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Mantle Cell Lymphoma (MCL)
Marginal Zone Lymphoma (MZL)
Waldenström's Macroglobulinemia (WM)
Diffuse Large B-cell Lymphoma
Follicular Lymphoma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-03-18
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: B-cell cancer is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The main objective of this study is to evaluate the safety and efficacy of ABBV-623 and ABBV-992 given alone and in combination in treating B-cell cancers. Adverse events, change in disease activity and how the drug moves through the body of adult participants with B-cell cancers will be evaluated.

ABBV-623 and ABBV-992 are investigational drugs being developed for the treatment of B-cell cancer. Study doctors assign participants to one of six groups, called treatment arms. Approximately 105 adult participants with a diagnosis of B-cell cancer will be enrolled in the study at approximately 50 sites worldwide.

Participants in the combination expansion treatment arms will receive oral tablets of ABBV-623 and/or ABBV-992 once daily for 24 months. All other arms are treated until progression.

Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be evaluated by medical assessments and blood tests. Adverse events will be collected and assessed throughout the clinical trial.


Eligibility criteria: Inclusion Criteria:

* Participants must have documented diagnosis for one of the following B-cell malignancies: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Waldenström's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), with measurable disease requiring treatment.
* Participants have relapsed or refractory to at least 2 prior systemic therapies.
* Combination Dose Expansion Only: Participants with documented diagnosis of CLL/SLL with measurable disease requiring treatment per by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* CLL/SLL, MCL, WM, MZL only: Prior Bruton's tyrosine kinase inhibitor (BTKi) exposure will be allowed if participant did not progress on active treatment and there is no evidence of resistance mutations.
* Renal, liver and hematological function lab values as determined in the protocol.
* For participants with prior BTK inhibitor exposure, no evidence of mutations which confer resistance to covalent BTK inhibitors.

Exclusion Criteria:

* Participants with indolent forms of non-Hodgkin lymphoma (NHL) that require immediate cytoreduction.
* Participants with prior B-cell lymphoma 2 (BCL2) inhibitor (BCL2i) exposure (except for participants in the ABBV-992 monotherapy cohort).

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 25 months.
measure: Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623
timeFrame: Up to approximately 96 weeks
measure: Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623
timeFrame: Up to approximately 96 weeks
measure: Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992
timeFrame: Up to approximately 96 weeks.
measure: Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992
timeFrame: Up to approximately 96 weeks
measure: Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Dose Escalation in Participants With R/R B-cell Malignancies: Percentage of Participants Achieving a Response of Partial Response (PR) or Better per Disease-Specific Response Criteria (e.g., IWCLL, Lugano, IWWM)
timeFrame: Up to approximately 2 years
measure: Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
timeFrame: Up to approximately 2 years
measure: Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better
timeFrame: Up to approximately 2 years
measure: Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
timeFrame: Up to approximately 2 years
measure: Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
timeFrame: Up to approximately 6 months
measure: Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
timeFrame: Up to approximately 1 Year
measure: Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD
timeFrame: Up to approximately 96 weeks
measure: Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better
timeFrame: Up to approximately 2 years
measure: Combination Dose Expansion in Participants With CLL/SLL: Time to Response
timeFrame: Up to approximately 2 years
measure: Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival
timeFrame: Approximately 2 years after study drug discontinuation
measure: Combination Dose Expansion in Participants With CLL/SLL: Overall Survival
timeFrame: Approximately 2 years after study drug discontinuation
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 226754
state: Tel-Aviv
city: Tel Aviv-Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 226755
state: Tel-Aviv
city: San Juan
country: Puerto Rico
facility: Hospital del Centro Comprensivo de Cancer de la UPR /ID# 225646
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 226087
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty /ID# 226085
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: