Clinical trial NCT05308654: 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
Official title: First-in-Human Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: Relapsed/Refractory Multiple Myeloma
ABBV-453
Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-04-04
Enrollment: 34
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: 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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria
timeFrame: Up to Approximately 12 Months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to Approximately 24 Months
measure: Depth of Response Minimal Residual Disease (MRD)
timeFrame: Up to Approximately 24 Months
measure: Progression Free Survival (PFS)
timeFrame: Up to Approximately 36 Months
measure: Overall Survival (OS)
timeFrame: Up to Approximately 36 Months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Med /ID# 242809
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center /ID# 243417
state: Florida
city: New Orleans
country: United States
facility: Tulane University School of Medicine /ID# 244854
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland /ID# 244858
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 242754
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester /ID# 242844
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center /ID# 243503
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Institute /ID# 243420
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr /ID# 242808
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health /ID# 244252
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 242842
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center /ID# 242810
state: Tennessee
city: Liverpool
country: Australia
facility: Liverpool Hospital /ID# 244826
state: New South Wales
city: Fitzroy Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne /ID# 244827
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Private Hospital Melbourne /ID# 262631
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health and Ludwig Institute for Cancer Research /ID# 248311
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare /ID# 248705
state: Victoria
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 250482
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 250483
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 250484
state: Yerushalayim
city: London
country: United Kingdom
facility: Barts Health NHS Trust /ID# 248972
state: London, City Of
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: