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)

Purpose

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 a dose escalation phase where participants will receive various doses of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of surzetoclax in combination with daratumumab + dexamethasone, or daratumumab + dexamethasone + pomalidomide (only during the expansion phase). In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. Approximately 130 adult participants with R/R MM will be enrolled in the study in approximately 40 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 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. 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.

Condition

  • Multiple Myeloma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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. - Substudy 1 Dose Escalation Cohorts and Substudy 2: -- Must be triple class exposed (PI, IMiD and anti-CD38) and have received 3 to 5 lines of prior antimyeloma therapy, and who have no other appropriate treatment options as deemed by the investigator. - Substudy 1 Dose Expansion Cohorts: - Must be double class exposed (PI, IMiD) and have received 1 to 3 lines of prior antimyeloma therapy.

Exclusion Criteria

  • Major surgery within 4 weeks of study treatment or planned during study participation. - Active infections: no recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled systemic infection. - Recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled active systemic infection.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Substudy 1: Dose Escalation ABBV-453 Combination 		Participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration.
  • Drug: ABBV-453
    Oral Tablet
  • Drug: Daratumumab
    Subcutaneous (SC) Injection
  • Drug: Dexamethasone
    Oral Tablet
Experimental
Substudy 1: Dose Expansion and Selection ABBV-453 Combination 		Participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, as part of the total 4.5 year study duration.
  • Drug: ABBV-453
    Oral Tablet
  • Drug: Daratumumab
    Subcutaneous (SC) Injection
  • Drug: Dexamethasone
    Oral Tablet
Active Comparator
Substudy 1: Dose Expansion and Selection Control 		Participants will receive daratumumab, dexamethasone, and pomalidomide, as part of the total 4.5 year study duration.
  • Drug: Daratumumab
    Subcutaneous (SC) Injection
  • Drug: Dexamethasone
    Oral Tablet
  • Drug: Pomalidomide
    Oral Capsule
Experimental
Substudy 2: Dose Escalation ABBV-453 Monotherapy 		Japanese participants will receive various doses of ABBV-453 as a monotherapy, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration.
  • Drug: ABBV-453
    Oral Tablet

Recruiting Locations

University of Southern California /ID# 272414
Los Angeles, California 90033

Yale University School of Medicine /ID# 272447
New Haven, Connecticut 06510

Dana-Farber Cancer Institute /ID# 271846
Boston, Massachusetts 02215

University of Michigan Health System - Ann Arbor /ID# 271536
Ann Arbor, Michigan 48109

Memorial Sloan Kettering Cancer Center - New York - York Avenue /ID# 271214
New York, New York 10065

University of North Carolina at Chapel Hill /ID# 272454
Chapel Hill, North Carolina 27514

Atrium Health Levine Cancer Institute /ID# 271510
Charlotte, North Carolina 28204

Wake Forest Baptist Health /ID# 271294
Winston-Salem, North Carolina 27103

Oregon Health and Science University /ID# 272282
Portland, Oregon 97239

University of Texas - Southwestern Medical Center /ID# 271914
Dallas, Texas 75235

Northwest Medical Specialties Tacoma /ID# 272506
Tacoma, Washington 98405

More Details

Status
Recruiting
Sponsor
AbbVie

Study Contact

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