Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM)

Celgene

Status and phase: Enrolling; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Bortezomib; Drug: Daratumumab; Drug: Iberdomide; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT04975997

U1111-1260-2872 (Other Identifier)

2020-000431-49 (EudraCT Number)

CC-220-MM-002

Details and patient eligibility

About

This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in combination with dexamethasone and daratumumab (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM).

Full description

This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in combination with dexamethasone and daratumumab (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM). Approximately 200 patients randomized in stage 1 to one of three iberdomide dose levels of 1, 1.3, or 1.6 mg in combination with daratumumab and dexamethasone (Treatment Arms A1, A2, or A3), or to the DVd comparator arm (Treatment Arm B).

In Stage 2 of the study, approximately 664 additional subjects will be randomized 1:1 between 2 treatment arms:

• Approximately 332 subjects will be randomized to receive Treatment Arm A (IberDd)
• Approximately 332 subjects will be randomized to receive Treatment Arm B (DVd)

Participants in both treatment arms will continue to receive treatment until confirmed progressive disease (PD), unacceptable toxicity or withdrawal of consent. To ensure accuracy and completeness of the primary endpoint assessment of progression-free survival (PFS), participants who permanently discontinue study treatment for any reason, other than confirmed PD or withdrawal of consent, will continue to be followed for disease assessment.

The study will be conducted in compliance with International Council for Harmonisation (ICH) and Good Clinical Practices (GCPs).

Enrollment: 864 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Documented diagnosis of multiple myeloma (MM) and measurable disease.
• Received 1 to 2 prior lines of anti-myeloma therapy.
• Must have documented disease progression during or after their last anti-myeloma regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

Exclusion Criteria

• Any condition that confounds the ability to interpret data from the study.
• Has plasma cell leukemia, Waldenstrom's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis.
• Known central nervous system involvement with MM.
• Prior therapy with iberdomide.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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864 participants in 4 patient groups

Daratumumab in combination with Iberdomide and dexamethasone - Dose 1

Experimental group

Description:

Participants will receive oral iberdomide, subcutaneous daratumumab and oral dexamethasone.

Treatment:

Drug: Dexamethasone

Drug: Iberdomide

Drug: Iberdomide

Drug: Daratumumab

Drug: Iberdomide

Daratumumab in combination with Iberdomide and dexamethasone - Dose 2

Experimental group

Treatment:

Drug: Dexamethasone

Drug: Iberdomide

Drug: Iberdomide

Drug: Daratumumab

Drug: Iberdomide

Daratumumab in combination with Iberdomide and dexamethasone - Dose 3

Experimental group

Treatment:

Drug: Dexamethasone

Drug: Iberdomide

Drug: Iberdomide

Drug: Daratumumab

Drug: Iberdomide

Daratumumab in combination with dexamethasone and bortezomib

Active Comparator group

Description:

Participants will receive subcutaneous daratumumab, bortezomib and oral dexamethasone

Treatment:

Drug: Dexamethasone

Drug: Daratumumab

Drug: Bortezomib