A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma

TeneoOne

Status and phase: Enrolling; Phase 1

Conditions: Relapsed/Refractory Multiple Myeloma

Treatments: Drug: Daratumumab; Drug: Nirogacestat; Drug: Lenalidomide; Drug: ABBV-383; Drug: Pomalidomide; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT05259839

M22-947

2021-005587-22 (EudraCT Number)

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 toxicity of ABBV-383 when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd), or nirogacestat (Niro) in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease activity will be assessed.

ABBV-383 is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. ABBV-383 co-administered with Pd, Rd, Dd, or Niro will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of ABBV-383, followed by a dose expansion phase to confirm the dose. Approximately 270 adult participants with R/R MM will be enrolled in the study in approximately 45 sites worldwide.

Participants will receive intravenous (IV) ABBV-383 co-administered with oral/IV Pd, oral/IV Rd, oral/IV/subcutaneous (SC) Dd, or oral/IV Niro in 28-day cycles.

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.

Enrollment: 270 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance of <= 2.
• Must have confirmed diagnosis of 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) criteria.
• Must have measurable disease as outlined in the protocol.
• Must be naïve to treatment with ABBV-383 and must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded.
• Has received prior MM treatment in Arms A, B, C, and D.

Exclusion criteria

• Received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment.

• Unresolved adverse event (AE)s >= Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from prior anticancer therapy.

• Known central nervous system involvement Multiple Myeloma (MM).

• Has any of the following conditions:

  • Nonsecretory MM.
  • Active Plasma cell leukemia i.e., either 20% of peripheral white blood cells or > 2.0 × 10^9L circulating plasma cells by standard differential.
  • Waldenstrom's macroglobulinemia.
  • Light chain amyloidosis.
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome.
  • Major surgery within 4 weeks prior to first dose or planned study participation.
  • Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal or antiviral).
  • Uncontrolled diabetes or hypertension within 14 days prior to first dose.
  • Peripheral neuropathy >= Grade 3 or >= Grade 2 with pain within 2 weeks prior to first dose.

• Known active infection of evidence of active hepatitis B, evidence of active hepatitis C, human immunodeficiency virus.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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270 participants in 4 patient groups

Arm A (ABBV-383 with Pomalidomide and Dexamethasone)

Experimental group

Description:

Participants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive ABBV-383 with Pomalidomide and Dexamethasone.

Treatment:

Drug: Dexamethasone

Drug: Pomalidomide

Drug: ABBV-383

Arm B (ABBV-383 with Lenalidomide and Dexamethasone)

Experimental group

Description:

Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Lenalidomide and Dexamethasone.

Treatment:

Drug: Dexamethasone

Drug: Lenalidomide

Drug: ABBV-383

Arm C (ABBV-383 with Daratumumab and Dexamethasone)

Experimental group

Description:

Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Daratumumab and Dexamethasone.

Treatment:

Drug: Dexamethasone

Drug: ABBV-383

Drug: Daratumumab

Arm D (ABBV-383 with Nirogacestat)

Experimental group

Description:

Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Nirogacestat.

Treatment:

Drug: ABBV-383

Drug: Nirogacestat