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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04804254




Registration number
NCT04804254
Ethics application status
Date submitted
16/03/2021
Date registered
18/03/2021
Date last updated
3/02/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-005196-12
Secondary ID [2] 0 0
M20-208
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-623
Treatment: Drugs - ABBV-992

Experimental: Monotherapy in Dose Escalation: ABBV-623 - Participants with Relapsed/Refractory (R/R) B-cell malignancies will receive escalating doses of ABBV-623.

Experimental: Monotherapy in Dose Escalation: ABBV-992 - Participants with R/R B-cell malignancies will receive escalating doses of ABBV-992.

Experimental: Combination in Dose Escalation - Participants with R/R B-cell malignancies will receive escalating doses of ABBV-623 and ABBV-992.

Experimental: Monotherapy in Dose Expansion: ABBV-623 - Participants with R/R B-cell malignancies will receive ABBV-623 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

Experimental: Monotherapy in Dose Expansion: ABBV-992 - Participants with R/R B-cell malignancies will receive ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.

Experimental: Combination in Dose Expansion - Participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) will receive ABBV-623 and ABBV-992 at recommended Phase 2 dose (RP2D) determined in dose escalation phase.


Treatment: Drugs: ABBV-623
Oral Tablets

Treatment: Drugs: ABBV-992
Oral Tablets

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
Up to approximately 25 months.
Primary outcome [2] 0 0
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-623
Timepoint [2] 0 0
Up to approximately 96 weeks
Primary outcome [3] 0 0
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-623
Timepoint [3] 0 0
Up to approximately 96 weeks
Primary outcome [4] 0 0
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of ABBV-992
Timepoint [4] 0 0
Up to approximately 96 weeks.
Primary outcome [5] 0 0
Dose Escalation: Area Under the Plasma Concentration- Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration of ABBV-992
Timepoint [5] 0 0
Up to approximately 96 weeks
Primary outcome [6] 0 0
Combination Dose Expansion: Overall Response Rate (ORR) (PR or Better by IWCLL Criteria) in Participants With R/R CLL/SLL
Timepoint [6] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Dose Escalation in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Dose Escalation in Participants With R/R B-cell Malignancies: Time to Response (TTR)
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Achievement of a Response of PR or Better
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Duration of Response (DOR) for Participants With a Response of PR or Better
Timepoint [5] 0 0
Up to approximately 2 years
Secondary outcome [6] 0 0
Monotherapy Dose Expansion in Participants With R/R B-cell Malignancies: Time to Response (TTR)
Timepoint [6] 0 0
Up to approximately 2 years
Secondary outcome [7] 0 0
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Timepoint [7] 0 0
Up to approximately 6 months
Secondary outcome [8] 0 0
Combination Dose Expansion in Participants With CLL/SLL: Achievement of Bone Marrow Undetectable Minimal Residual Disease (uMRD)
Timepoint [8] 0 0
Up to approximately 1 Year
Secondary outcome [9] 0 0
Combination Dose Expansion in Participants With CLL/SLL: Percentage of Participants With Achievement of Peripheral Blood uMRD
Timepoint [9] 0 0
Up to approximately 96 weeks
Secondary outcome [10] 0 0
Combination Dose Expansion in Participants With CLL/SLL: Duration of Response for Participants With a Response of PR or Better
Timepoint [10] 0 0
Up to approximately 2 years
Secondary outcome [11] 0 0
Combination Dose Expansion in Participants With CLL/SLL: Time to Response
Timepoint [11] 0 0
Up to approximately 2 years
Secondary outcome [12] 0 0
Combination Dose Expansion in Participants with CLL/SLL: Progression Free Survival
Timepoint [12] 0 0
Approximately 2 years after study drug discontinuation
Secondary outcome [13] 0 0
Combination Dose Expansion in Participants With CLL/SLL: Overall Survival
Timepoint [13] 0 0
Approximately 2 years after study drug discontinuation

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Tel-Aviv
Country [2] 0 0
Puerto Rico
State/province [2] 0 0
San Juan
Country [3] 0 0
Turkey
State/province [3] 0 0
Ankara
Country [4] 0 0
Turkey
State/province [4] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04804254
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04804254