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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/NCT05308654




Registration number
NCT05308654
Ethics application status
Date submitted
25/03/2022
Date registered
4/04/2022
Date last updated
25/01/2024

Titles & IDs
Public title
A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets
Scientific title
First-in-Human Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2022-501685-22-01
Secondary ID [2] 0 0
M21-406
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-453
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Daratumumab
Treatment: Drugs - Lenalidomide

Experimental: Part 1: Monotherapy Dose Escalation - Participants with relapsed or refractory (R/R) multiple myeloma (MM) will receive escalating doses of ABBV-453, until the maximum tolerated dose (MTD) is determined.

Experimental: Part 2: Arm 1 - Participants will receive continuous doses of ABBV-453 in combination with dexamethasone in 28-day cycles.

Experimental: Part 2: Arm 2 - Participants will receive continuous doses of ABBV-453 in combination with daratumumab and dexamethasone in 28-day cycles.

Experimental: Part 2: Arm 3 - Participants will receive continuous doses of ABBV-453 in combination with daratumumab, lenalidomide, and dexamethasone in 28-day cycles.

Experimental: Japan Cohort - Participants with R/R MM will receive escalating doses of ABBV-453, until the MTD is determined.


Treatment: Drugs: ABBV-453
Oral; Tablet

Treatment: Drugs: Dexamethasone
Oral Tablet

Treatment: Drugs: Daratumumab
Subcutaneous Injection

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

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria
Timepoint [1] 0 0
Up to Approximately 12 Months
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Up to Approximately 24 Months
Secondary outcome [2] 0 0
Depth of Response Minimal Residual Disease (MRD)
Timepoint [2] 0 0
Up to Approximately 24 Months
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
Up to Approximately 36 Months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Up to Approximately 36 Months

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status <= 1.

- Laboratory values meeting the criteria outlined in the protocol.

- Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma
Working Group (IMWG) criteria.

- Has measurable disease at screening as defined in the protocol.

- Locally documented or centrally determined t(11;14) positive status and/or centrally
determined BCL2high status. Note: If local testing for t(11;14) is discordant with
central testing for t(11;14) status, a detailed review of central and local results
for t(11;14) status is required to ensure the participants' safety.

- Part 1 and Part 2, Arm 1 Only: Refractory to or intolerant of all established MM
therapies that are known to provide clinical benefit and are triple class exposed to a
proteasome inhibitors (PI), an Immunomodulatory drugs (IMID), and an anti-CD38
monoclonal antibody in previous line(s) of therapy.

- Part 2, Arms 2 and 3 Only: Received 1 to 3 prior lines of therapy, including a PI or
an IMiD.

- Part 1 only: Permitted to be venetoclax or BCL-2 inhibitor exposed in previous lines
of therapy.

- Life expectancy >= 12 weeks.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinically relevant or significant Electrocardiogram (ECG) abnormalities as outlined
in the protocol.

- Part 2 only: Previous treatment with venetoclax or BCL-2 inhibitor.

- Part 2, Arms 2 and 3 only: Prior daratumumab or other anti-CD38 therapy exposure that
meets any of the criteria outlined in the protocol.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/08/2026
Actual
Sample size
Target
360
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital /ID# 244826 - Liverpool
Recruitment hospital [2] 0 0
St Vincent's Hospital Melbourne /ID# 244827 - Fitzroy Melbourne
Recruitment hospital [3] 0 0
St. Vincent's Private Hospital Melbourne /ID# 262631 - Fitzroy
Recruitment hospital [4] 0 0
Austin Health and Ludwig Institute for Cancer Research /ID# 248311 - Heidelberg
Recruitment hospital [5] 0 0
Epworth Healthcare /ID# 248705 - Richmond
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy Melbourne
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
Israel
State/province [11] 0 0
Tel-Aviv
Country [12] 0 0
Israel
State/province [12] 0 0
Yerushalayim
Country [13] 0 0
United Kingdom
State/province [13] 0 0
London, City Of

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

Ethics approval
Ethics application status

Summary
Brief summary
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma
cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of
ABBV-453 in adult participants with relapsed/refractory (R/R) MM. Adverse events and change
in disease activity will be assessed.

ABBV-453 is an investigational drug being developed for the treatment of R/R MM. Part 1 will
be a monotherapy dose escalation phase to determine the best dose of ABBV-453. In Part 2,
participants are placed in 1 of 3 groups called treatment arms. Each group receives a
different treatment. Approximately 28 to 48 adult participants in Part 1 and 150 to 312 adult
participants in Part 2 with R/R MM will be enrolled in the study in approximately 70 sites
worldwide.

In Part 1 and the Japan Cohort, Participants will receive oral ABBV-453 tablets once daily
(QD) in 28-day cycles. In Part 2, Arm 1, participants will receive continuous doses of oral
ABBV-453 tablets QD in combination with oral dexamethasone tablets once weekly in 28-day
cycles. In Part 2, Arm 2, participants will receive continuous doses of oral ABBV-453 tablets
QD in combination with subcutaneous injections of daratumumab every 1 to 4 weeks and oral
dexamethasone tablets once weekly in, 28-day cycles. In Part 2, Arm 3, participants will
receive continuous doses of oral ABBV-453 tablets QD in combination with subcutaneous
injections of daratumumab every 1 to 4 weeks, oral lenalidomide capsules QD on Days 1-21, and
oral dexamethasone tablets once weekly, in 28-day cycles.

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 an approved
institution (hospital or clinic). The effect of the treatment will be frequently checked by
medical assessments, blood tests, and side effects.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05308654
Trial related presentations / publications
Public notes

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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05308654