A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)

NCT06953960
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
325
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Lead sponsor
AbbVie
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Start date
2025-07-23
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Number of sites
51
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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 change in disease activity of surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed. Surzetoclax is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be dose escalation and dose expansion phases where participants will receive various doses (escalation) or 1 of 2 doses (expansion) of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. In Substudy 3 there will be dose escalation and optimization phases where participants will receive various doses (escalation) or 1 of 2 doses (optimization) of of surzetoclax and etentamig to determine the best dose of surzetoclax and etentamig. Optimization will also include etentamig received alone. Approximately 325 adult participants with R/R MM will be enrolled in the study in approximately 55 sites worldwide. In Substudy 1 escalation phase, participants will receive oral surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive 1 of 2 doses oral surzetoclax tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral surzetoclax tablets. In Substudy 3 escalation phase, participants will receive oral surzetoclax tablets in combination with IV etentamig and in the expansion phase, will receive 1 of 2 doses of both oral surzetoclax tablets in combination with of IV etentamig, or IV etentamig alone. The total study duration is approximately 4.5 years. 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. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.
clinicaltrials.gov
Short title
A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)
clinicaltrials.gov
Official title
A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of the BCL-2 Inhibitor Surzetoclax (ABBV-453) Given as Monotherapy or in Combination With Antimyeloma Regimens in Subjects With Multiple Myeloma
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2030-12-01
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First posted
2025-05-01
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Registry last updated
2026-10-27
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Primary completion date
2030-12-01
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Start date
2025-07-23
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Participants
325
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Participant count basis
Estimated
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Planned participants
325
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Protocol amendments
3
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Number of sites
51
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
AbbVie
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06953960
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ClinicalTrials.gov ID
NCT06953960
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Dose-Limiting Toxicities (DLT)s of ABBV-453

    Timeframe: Up to Approximately 45 Months

    DLT events are defined as specific clinically significant adverse events or abnormal laboratory values assessed as events regardless of attribution to ABBV-453, except those clearly and incontrovertibly associated with underlying disease or extraneous causes.

  2. Number of Participants with Adverse Events (AE)s

    Timeframe: Up to Approximately 4.5 Years

    An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

  1. Overall Response Rate (ORR)

    Timeframe: Up to Approximately 4.5 Years

    ORR is defined as the percentage of participants with a confirmed partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) per Investigator review according to International Myeloma Working Group (IMWG) 2016 criteria.

  2. Progression-Free Survival (PFS)

    Timeframe: Up to Approximately 4.5 Years

    PFS is defined as time from first study treatment to the earliest documented disease progression according to IMWG 2016 criteria, as determined by the investigator, or death due to any cause, whichever occurs earlier.

  3. Duration of Response (DOR)

    Timeframe: Up to Approximately 4.5 Years

    DOR is defined as the time from the date of achieving the first confirmed sCR/CR/VGPR/PR to the date of recurrence, disease progression according to IMWG 2016 criteria, as determined by the investigator, or death of any cause, whichever occurs earlier.

  4. Time-to-Progression (TTP)

    Timeframe: Up to Approximately 4.5 Years

    TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.

  5. Time to Next Treatment

    Timeframe: Up to Approximately 4.5 Years

    Time to next treatment will be defined as the number of days from the date of first dose to the date of next treatment.

  6. Minimal Residual Disease (MRD) Negativity

    Timeframe: Up to Approximately 4.5 Years

    MRD negativity is defined as having less than 1 myeloma cell that may remain in the bone marrow aspirate per 10\^5 nucleated cells. Rate of MRD negativity will be determined.

  7. Overall Survival (OS)

    Timeframe: Up to Approximately 4.5 Years

    OS is defined as time from first study treatment to death due to any cause.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.

  • All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:

    • Serum M-protein >= 0.5 g/dL (>= 5g/L); OR
    • Urine M-protein >= 200 mg/24 hours; OR
    • For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) >= 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.

  • B-cell lymphoma (BCL)-2 inhibitor treatment naïve.

  • t(11;14) positive status and/or BCL2 high status.

  • Must have confirmed diagnosis of relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen, based on the investigator's determination of the international myeloma working group (IMWG) 2016 criteria.

  • Major surgery within 4 weeks of study treatment or planned during study participation.
  • Recent infection requiring systemic treatment that was completed <= 14 days before first dose of study treatment and/or uncontrolled active systemic infection.
Sources for eligibility
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  • University of Southern California /ID# 272414Los Angeles, United StatesRecruiting
  • Yale University School of Medicine /ID# 272447New Haven, United StatesRecruiting
  • Dana-Farber Cancer Institute /ID# 271846Boston, United StatesRecruiting
  • University of Michigan Health System - Ann Arbor /ID# 271536Ann Arbor, United StatesRecruiting
  • Memorial Sloan Kettering Cancer Center - New York - York Avenue /ID# 271214New York, United StatesRecruiting
  • Atrium Health Levine Cancer Institute /ID# 271510Charlotte, United StatesRecruiting
  • University Of North Carolina Health Care - Hillsborough Campus /ID# 272454Hillsborough, United StatesRecruiting
  • Atrium Health Wake Forest Baptist Medical Center /ID# 271294Winston-Salem, United StatesRecruiting
  • Oregon Health and Science University /ID# 272282Portland, United StatesRecruiting
  • University of Texas - Southwestern Medical Center /ID# 271914Dallas, United StatesRecruiting
  • Huntsman Cancer Institute /ID# 271618Salt Lake City, United StatesRecruiting
  • Northwest Medical Specialties Tacoma /ID# 272506Tacoma, United StatesRecruiting
  • Liverpool Hospital /ID# 272002Liverpool, AustraliaRecruiting
  • Calvary Mater Newcastle /ID# 272498Waratah, AustraliaRecruiting
  • St Vincent's Hospital - Melbourne /ID# 271997Fitzroy, AustraliaRecruiting
  • Epworth HealthCare /ID# 272497Richmond, AustraliaRecruiting
  • UZ Gent /ID# 271432Ghent, BelgiumRecruiting
  • Universitair Ziekenhuis Leuven /ID# 272382Leuven, BelgiumRecruiting
  • CHU de Liege /ID# 271430Liège, BelgiumRecruiting
  • CHU de Montpellier - Hopital Saint Eloi /ID# 275570Montpellier, FranceRecruiting
  • Centre Hospitalier Universitaire de Poitiers /ID# 275563Poitiers, FranceRecruiting
  • IUCT Oncopole /ID# 275568Toulouse, FranceRecruiting
  • Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 275562Nantes, FranceRecruiting
  • Hopital Universitaire Necker Enfants Malades /ID# 275571Paris, FranceRecruiting
  • Universitaetsklinikum Heidelberg /ID# 275598Heidelberg, GermanyRecruiting

And 26 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2024-517140-65-00
  • 2024-517140-65
Sources for references
clinicaltrials.gov

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