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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Daratumumab; Drug: Dexamethasone; Drug: ABBV-453; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital /ID# 244826
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St. Vincent's Private Hospital Melbourne /ID# 262631
    • Fitzroy Melbourne, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital Melbourne /ID# 244827
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health and Ludwig Institute for Cancer Research /ID# 248311
    • Richmond, Victoria, Australia, 3121
      • Recruiting
      • Epworth Healthcare /ID# 248705
• Israel
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 250482
    • Tel Aviv, Tel-Aviv, Israel, 6423906
      • Recruiting
      • Tel Aviv Sourasky Medical Center /ID# 250483
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Recruiting
      • Hadassah Medical Center-Hebrew University /ID# 250484
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, E1 2ES
      • Recruiting
      • Barts Health NHS Trust /ID# 248972
• United States
  • California
    • Stanford, California, United States, 94305-2200
      • Recruiting
      • Stanford University School of Med /ID# 242809
  • Florida
    • Miami, Florida, United States, 33136-1002
      • Recruiting
      • Sylvester Comprehensive Cancer Center /ID# 243417
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2699
      • Recruiting
      • Tulane University /ID# 244854
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • American Oncology Partners of Maryland, PA /ID# 244858
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 242754
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Recruiting
      • Mayo Clinic - Rochester /ID# 242844
  • New York
    • New York, New York, United States, 10065-6007
      • Recruiting
      • Memorial Sloan Kettering Cancer Center /ID# 243503
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514-4220
      • Recruiting
      • Univ NC Chapel Hill /ID# 243420
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Univ Med Ctr /ID# 242808
    • Winston-Salem, North Carolina, United States, 27157-0001
      • Recruiting
      • Wake Forest Baptist Health /ID# 244252
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-2640
      • Recruiting
      • Penn Presbyterian Medical Center /ID# 242842
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0021
      • Recruiting
      • Vanderbilt Ingram Cancer Center /ID# 242810

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 2: Arm 1; Participants will receive continuous doses of ABBV-453 in combination with dexamethasone in 28-day cycles.	Drug: Dexamethasone; Oral Tablet; Drug: ABBV-453; Oral; Tablet
Experimental: Part 2: Arm 2; Participants will receive continuous doses of ABBV-453 in combination with daratumumab and dexamethasone in 28-day cycles.	Drug: Daratumumab; Subcutaneous Injection; Drug: Dexamethasone; Oral Tablet; Drug: ABBV-453; Oral; Tablet
Experimental: Part 2: Arm 3; Participants will receive continuous doses of ABBV-453 in combination with daratumumab, lenalidomide, and dexamethasone in 28-day cycles.	Drug: Daratumumab; Subcutaneous Injection; Drug: Dexamethasone; Oral Tablet; Drug: ABBV-453; Oral; Tablet; Drug: Lenalidomide; Oral Capsule
Experimental: Japan Cohort; Participants with R/R MM will receive escalating doses of ABBV-453, until the MTD is determined.	Drug: ABBV-453; Oral; Tablet
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.	Drug: ABBV-453; Oral; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): August 28, 2026

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Relapsed/Refractory Multiple Myeloma; ABBV-453
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Daratumumab
• Other Study ID Numbers: M21-406; 2022-501685-22-01 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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