Clinical trial NCT06953960: A Study to Assess Adverse Events and Change in Disease Activity of Oral ABBV-453 Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)
Official title: A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of the BCL-2 Inhibitor ABBV-453 Given as Monotherapy or in Combination With Antimyeloma Regimens in Subjects With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
ABBV-453
Daratumumab
Dexamethasone
Pomalidomide
Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2025-05-01
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 change in disease activity 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. In Substudy 1 there will be a dose escalation phase where participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of ABBV-453 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 ABBV-453 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 ABBV-453 tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral ABBV-453 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 ABBV-453 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose-Limiting Toxicities (DLT)s of ABBV-453
timeFrame: Up to Approximately 45 Months
measure: Number of Participants with Adverse Events (AE)s
timeFrame: Up to Approximately 4.5 Years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to Approximately 4.5 Years
measure: Progression-Free Survival (PFS)
timeFrame: Up to Approximately 4.5 Years
measure: Duration of Response (DOR)
timeFrame: Up to Approximately 4.5 Years
measure: Time-to-Progression (TTP)
timeFrame: Up to Approximately 4.5 Years
measure: Time to Next Treatment
timeFrame: Up to Approximately 4.5 Years
measure: Minimal Residual Disease (MRD) Negativity
timeFrame: Up to Approximately 4.5 Years
measure: Overall Survival (OS)
timeFrame: Up to Approximately 4.5 Years
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: