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)

AbbVie

Status and phase: Begins enrollment this month; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: ABBV-453; Drug: Daratumumab; Drug: Pomalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06953960

M25-275

2024-517140-65 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

130 participants in 4 patient groups

Substudy 1: Dose Escalation ABBV-453 Combination

Experimental group

Description:

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.

Treatment:

Drug: Daratumumab

Drug: ABBV-453

Drug: Dexamethasone

Substudy 1: Dose Expansion and Selection ABBV-453 Combination

Experimental group

Description:

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.

Treatment:

Drug: Daratumumab

Drug: ABBV-453

Drug: Dexamethasone

Substudy 1: Dose Expansion and Selection Control

Active Comparator group

Description:

Participants will receive daratumumab, dexamethasone, and pomalidomide, as part of the total 4.5 year study duration.

Treatment:

Drug: Pomalidomide

Drug: Daratumumab

Drug: Dexamethasone

Substudy 2: Dose Escalation ABBV-453 Monotherapy

Experimental group

Description:

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.

Treatment:

Drug: ABBV-453