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

• ClinicalTrials.gov Identifier: NCT05308654
• Recruitment Status: Recruiting
• First Posted: April 4, 2022
• Last Update Posted: January 25, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: March 25, 2022
• First Posted Date: April 4, 2022
• Last Update Posted Date: January 25, 2024
• Actual Study Start Date: May 17, 2022
• Estimated Primary Completion Date: August 28, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2024)

Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) Criteria [ Time Frame: Up to Approximately 12 Months ]

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).

Original Primary Outcome Measures (submitted: March 25, 2022)

Overall Response Rate (ORR) per Adapted International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to Approximately 12 Months ]

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).

Current Secondary Outcome Measures (submitted: October 13, 2023)

• Duration of Response (DOR) [ Time Frame: Up to Approximately 24 Months ]
  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.
• Depth of Response Minimal Residual Disease (MRD) [ Time Frame: Up to Approximately 24 Months ]
  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.
• Progression Free Survival (PFS) [ Time Frame: Up to Approximately 36 Months ]
  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.
• Overall Survival (OS) [ Time Frame: Up to Approximately 36 Months ]
  Overall survival (OS) is defined as time from first study treatment to death due to any cause.

Original Secondary Outcome Measures (submitted: March 25, 2022)

• Duration of Response (DOR) [ Time Frame: Up to Approximately 24 Months ]
  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.
• Depth of Response Minimal Residual Disease (MRD) [ Time Frame: Up to Approximately 24 Months ]
  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 adapted IMWG criteria.
• Progression Free Survival (PFS) [ Time Frame: Up to Approximately 36 Months ]
  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.
• Overall Survival (OS) [ Time Frame: Up to Approximately 36 Months ]
  Overall survival (OS) is defined as time from first study treatment to death due to any cause.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Relapsed/Refractory Multiple Myeloma

Intervention

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

Study Arms

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

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

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

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 13, 2023): 360
• Original Estimated Enrollment (submitted: March 25, 2022): 21
• Estimated Study Completion Date: August 28, 2026
• Estimated Primary Completion Date: August 28, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Israel, United Kingdom, United States
• Removed Location Countries: Canada, France, Germany, Spain, Sweden

Administrative Information

• NCT Number: NCT05308654
• Other Study ID Numbers: M21-406; 2022-501685-22-01 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: January 2024