A Study to Assess Adverse Events of Intravenously (IV) Infused ABBV-383 in Adult Participants With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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Multiple Myeloma (MM) is a cancer of the blood's plasma cells ( blood cell). The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine adverse events and change in disease symptoms of ABBV-383 in adult participants with relapsed/refractory (R/R) MM. ABBV-383 is an investigational drug being developed for the treatment of R/R Multiple Myeloma (MM). This study is broken into 2 Arms; Arm A (Parts 1 and 2) and Arm B. Arm A includes 2 parts: step-up dose optimization (Part 1) and dose expansion (Part 2). In Part 1, different level of step-up doses are tested followed by the target dose of ABBV-383. In Part 2, the step-up dose identified in Part 1 (Dose A) will be used followed by the target dose A of ABBV-383. In Arm B a flat dose of ABBV-383 will be tested. Around 120 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 30 sites across the world. Participants will receive ABBV-383 as an infusion into the vein in 28 day cycles for approximately 3 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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.

Official Title
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A Multicenter, Phase 1b, Open-label Study to Evaluate Dose Optimization Measures and Safety of ABBV-383 in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: ABBV-383


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have measurable disease as outlined in the protocol. Eastern Cooperative Oncology Group (ECOG) performance of <= 2. Relapsed/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. Must be naïve to treatment with ABBV-383. Arm A: Must have received at least 3 or more lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory imide drug (IMiD), and an anti-CD38 monoclonal antibody. Arm B: Must have received at least 2 or more lines of therapy, including exposure to a PI, an IMiD, an anti-CD38 monoclonal antibody, and a prior B-cell maturation antigen (BCMA)-targeted therapy (anti-drug conjugate [ADC] or chimeric antigen receptor T-cell [CAR-T] directed against BCMA). Exclusion Criteria: - Arm A: Received BCMA-targeted therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Part 1): ABBV-383 Dose Escalation<br>B-cell maturation antigen (BCMA) naïve participants will receive different doses of ABBV-383 in 28 day cycles. | Drug: ABBV-383<br>* Intravenous Infusion<br>|
| Experimental: Arm A (Part 2): ABBV-383 Dose Expansion<br>BCMA naïve participants will receive the dose of ABBV-383 dose A in 28 day cycles. | Drug: ABBV-383<br>* Intravenous Infusion<br>|
| Experimental: Arm B: ABBV-383 Dose Expansion<br>Participants previously exposed to BCMA-targeted agents will receive ABBV-383 Dose A in 28 day cycles. | Drug: ABBV-383<br>* Intravenous Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm A (Part 1 and Part 2): Number of Grade >= 2 Cytokine Release Syndrome (CRS) Events | CRS is defined by fever, hypoxia, and hypotension and graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines | Up to Day 28 | 
| Arm B: Number of Adverse Events (AEs) of Special Interest (CRS and Immune Effector Cell-associated Neurotoxicity Syndrome [ICANS]) | AEs of special interest will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) 2019 guidelines. All other AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm A: Number of Cytokine Release Syndrome (CRS) Events | CRS is defined by fever, hypoxia, and hypotension and graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines | Up to 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Cancer, ABBV-383, B-Cell Maturation Antigen