A Study to Evaluate Adverse Events, Change in Disease Activity, Tolerability, and How Intravenous ABBV-438 Moves Through the Body in Adult Participants With Multiple Myeloma (MM)

Official title

A Phase 1, First-in-Human, Open Label Study Evaluating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ABBV-438 in Adult Subjects With Relapsed or Refractory Multiple Myeloma

Overview

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, tolerability, and how ABBV-438 moves through the body, in adult participants with relapsed/refractory (R/R) MM. Adverse events, tolerability, how ABBV-438 moves through the body will be assessed. ABBV-438 is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms broken into 2 parts. ABBV-438 will be given alone and multiple doses will be explored. This study will include a dose escalation phase (Part 1) to determine the best dose of ABBV-438, followed by a dose expansion phase (Part 2) to confirm the dose. Approximately 127 adult participants with R/R MM will be enrolled in the study in approximately 24 sites worldwide. Participants will receive intravenous (IV) ABBV-438 alone first in multiple doses in the dose escalation phase (Part 1); then in 1 of 2 doses from Part 1 in the dose expansion phase (Part 2). The overall study duration will be approximately 69.5 months. 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 (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Interventions

• Drug ABBV-438
  Intravenous (IV)

Primary outcome measures

• Number of Participants With Adverse Events (AE) [Time frame: Up to Approximately 69.5 Months]
• Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters [Time frame: Up to Approximately 69.5 Months]
• Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters [Time frame: Up to Approximately 69.5 Months]
• Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) [Time frame: Up to Approximately 69.5 Months]

Secondary outcome measures (9)

• Overall Response Rate (ORR) [Time frame: Up to Approximately 69.5 Months]
• Number of Participants Achieving VGPR or Better [Time frame: Up to Approximately 69.5 Months]
• Duration of Response (DOR) in Participants who Achieved PR or VGPR or CR or sCR [Time frame: Up to Approximately 69.5 Months]
• Progression-free survival (PFS) [Time frame: Up to Approximately 69.5 Months]
• Overall survival (OS) [Time frame: Up to Approximately 69.5 Months]
• Area Under the Plasma Concentration-Time Curve (AUC) of ABBV-438 [Time frame: Up to Approximately 69.5 Months]
• Maximum Observed Plasma Concentration (Cmax) of ABBV-438 [Time frame: Up to Approximately 69.5 Months]
• Time to Cmax (Tmax) of ABBV-438 [Time frame: Up to Approximately 69.5 Months]
• t1/2 (Half-life) of ABBV-438 [Time frame: Up to Approximately 69.5 Months]

Eligibility criteria

Inclusion criteria

• Has relapsed or refractory 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 standard International Myeloma Working Group (IMWG) (2016) response criteria:

• Relapsed defined as previously treated myeloma that progresses and requires initiation of salvage therapy;
• Refractory defined as disease that is nonresponsive (failure to achieve minimal response) while on last therapy, or progresses within 60 days of last therapy.
• Has measurable disease at screening, defined by at least 1 of the following within 28 days prior to enrollment:

• Serum M-protein >= 0.5 g/dL (>=5 g/L); OR;
• Urine M-protein >= 200 mg/24 hours; OR;
• Involved serum free light chain (sFLC) >= 10 mg/dL (100mg/L), provided serum FLC ratio is abnormal;
• Must have had 3 or more prior lines of therapy with exposure to a proteasome inhibitor (PI), an immunomodulatory imide drugs (IMiD), and an anti-CD38 therapy and are intolerant to, or unable to access, available therapies that are known to confer clinical benefit to participants with relapsed or refractory (R/R) MM. Note: A line of therapy consists of relapsed or refractory 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.

Exclusion criteria

• Known history of Central Nervous System involvement by MM.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• City of Hope National Medical Center /ID# 280273 — Duarte
• City of Hope - Orange County Lennar Foundation Cancer Center /ID# 279067 — Irvine
• Colorado Blood Cancer Institute /ID# 280275 — Denver
• City Of Hope - Atlanta. /ID# 280294 — Newnan
• START Midwest /ID# 279035 — Grand Rapids

Israel · 3 centers

• The Chaim Sheba Medical Center /ID# 279065 — Ramat Gan
• Tel Aviv Sourasky Medical Center /ID# 279066 — Tel Aviv
• Hadassah Medical Center-Hebrew University /ID# 278865 — Jerusalem

Japan · 1 center

• The Cancer Institute Hospital Of JFCR /ID# 279069 — Koto-ku

Identifiers

NCT: NCT07409246 · M25-025 · 2025-523517-29

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗