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

Relapsed/Refractory Multiple Myeloma Clinical Trial

Official title:

First-in-Human Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05308654
• Other study ID #: M21-406
• Secondary ID: 2022-501685-22-0
• Status: Recruiting
• Phase: Phase 1
• Start date: May 17, 2022
• Est. completion date: August 28, 2026

Study information

• Verified date: January 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: August 28, 2026
• Est. primary completion date: August 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Drug:
• ABBV-453
Oral; Tablet
• Dexamethasone
Oral Tablet
• Daratumumab
Subcutaneous Injection
• Lenalidomide
Oral Capsule

Locations

Country	Name	City	State
Australia	St. Vincent's Private Hospital Melbourne /ID# 262631	Fitzroy	Victoria
Australia	St Vincent's Hospital Melbourne /ID# 244827	Fitzroy Melbourne	Victoria
Australia	Austin Health and Ludwig Institute for Cancer Research /ID# 248311	Heidelberg	Victoria
Australia	Liverpool Hospital /ID# 244826	Liverpool	New South Wales
Australia	Epworth Healthcare /ID# 248705	Richmond	Victoria
Israel	Hadassah Medical Center-Hebrew University /ID# 250484	Jerusalem	Yerushalayim
Israel	The Chaim Sheba Medical Center /ID# 250482	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 250483	Tel Aviv	Tel-Aviv
United Kingdom	Barts Health NHS Trust /ID# 248972	London	London, City Of
United States	University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 242754	Ann Arbor	Michigan
United States	American Oncology Partners of Maryland, PA /ID# 244858	Bethesda	Maryland
United States	Univ NC Chapel Hill /ID# 243420	Chapel Hill	North Carolina
United States	Duke Univ Med Ctr /ID# 242808	Durham	North Carolina
United States	Sylvester Comprehensive Cancer Center /ID# 243417	Miami	Florida
United States	Vanderbilt Ingram Cancer Center /ID# 242810	Nashville	Tennessee
United States	Tulane University /ID# 244854	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center /ID# 243503	New York	New York
United States	Penn Presbyterian Medical Center /ID# 242842	Philadelphia	Pennsylvania
United States	Mayo Clinic - Rochester /ID# 242844	Rochester	Minnesota
United States	Stanford University School of Med /ID# 242809	Stanford	California
United States	Wake Forest Baptist Health /ID# 244252	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria	ORR is defined as the percentage of participants with a confirmed best overall response (BOR) of partial response (PR) + very good partial response (VGPR) + complete response (CR) + stringent complete response (sCR) as assessed by investigators per adapted IMWG criteria for relapsed or refractory (R/R) multiple myeloma (MM).	Up to Approximately 12 Months
Secondary	Duration of Response (DOR)	DOR is defined for participants achieving a confirmed sCR/CR/VGPR/PR as the time from the initial response of sCR/CR/VGPR/PR per investigator review according to adapted IMWG criteria to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately 24 Months
Secondary	Depth of Response Minimal Residual Disease (MRD)	MRD negativity is defined as having less than 1 myeloma cell that may remain in the bone marrow aspirate. Depth of response is defined as the proportion of MRD negativity for participants achieving a confirmed sCR/CR per investigator review according to IMWG criteria.	Up to Approximately 24 Months
Secondary	Progression Free Survival (PFS)	PFS is defined as time from first study treatment to a documented disease progression according to adapted IMWG criteria, as determined by the investigator, or death due to any cause, whichever occurs earlier.	Up to Approximately 36 Months
Secondary	Overall Survival (OS)	Overall survival (OS) is defined as time from first study treatment to death due to any cause.	Up to Approximately 36 Months