Study to Determine Recommended Phase 2 Dose of Intravenous (IV) Eftozanermin Alfa in Combination With IV or Subcutaneous (SC) Bortezomib and Oral Dexamethasone Tablet and to Assess Change in Disease Symptoms in Adult Participants With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT04570631

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-05
• Study Completion Date: 2025-05-05

Brief Summary

Multiple myeloma (MM) is a rare cancer caused by abnormal survival of plasma cells (blood cells). Most trial participants with MM relapse (cancer has come back) or become non- responsive to treatment and remission gets shorter after each line of treatment. This is a study to determine recommended Phase 2 dose and change in disease symptoms of eftozanermin alfa in combination with bortezomib and dexamethasone to assess how efficient the treatment is in adult participants with relapsed/refractory (R/R) MM.

Eftozanermin alfa (ABBV-621) is an investigational drug being developed for the treatment of R/R Multiple Myeloma (MM). Study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. Participants in one arm will receive different doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine phase 2 dose (RP2D). Participants in the other arm will receive eftozanermin alfa at RP2D in combination with bortezomib and dexamethasone. Around 40 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 20 sites across the world.

Participants will receive eftozanermin alfa as an infusion into the vein in combination with bortezomib as an infusion into the vein or an injection under the skin and oral dexamethasone tablets for 12 cycles. Each cycle is 21 days for cycles 1-8 and 35 days for cycles 9-12.

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Safety Lead-in

Participants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).

Group Type: EXPERIMENTAL

Eftozanermin alfa

Intervention Type: DRUG

Intravenous (IV) infusion

Bortezomib

Intervention Type: DRUG

Intravenous (IV) or Subcutaneous (SC) injection

Dexamethasone

Intervention Type: DRUG

Oral Tablet

Dose Expansion

Participants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.

Group Type: EXPERIMENTAL

Eftozanermin alfa

Intervention Type: DRUG

Intravenous (IV) infusion

Bortezomib

Intervention Type: DRUG

Intravenous (IV) or Subcutaneous (SC) injection

Dexamethasone

Intervention Type: DRUG

Oral Tablet

Interventions

Eftozanermin alfa

Intravenous (IV) infusion

Intervention Type: DRUG

Bortezomib

Intravenous (IV) or Subcutaneous (SC) injection

Intervention Type: DRUG

Dexamethasone

Oral Tablet

Intervention Type: DRUG

Other Intervention Names

ABBV-621

Eligibility Criteria

Inclusion Criteria

• Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria.
• Has measurable disease at screening, defined by at least 1 of the following:

• Serum M-protein >= 1.0 g/dL (>= 10 g/L); OR
• Urine M-protein >= 200 mg/24 hours; OR
• Serum free light chain (sFLC) >= 10 mg/dL (100 mg/L), provided serum FLC ratio is abnormal.
• Relapsed or refractory MM after receiving at least 3, but no more than 6 prior lines of therapy, including an immunomodulatory agent (IMiD), proteasome inhibitor (PI), and an anti-CD38 antibody, and has documented disease progression that occurred during or after the most recent therapy.
• Has adequate hematologic, hepatic and renal function as defined in the protocol.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Life expectancy >= 12 weeks.

Exclusion Criteria

• Received bortezomib as part of the most recent prior therapy.
• Has primary refractory disease defined as disease that is non-responsive.
• Has not achieved a minimal response or better per IMWG criteria with any therapy.
• Has discontinued bortezomib due to toxicity.
• History of chronic liver disease or significant unresolved liver disease; currently active (within the last 6 months) hepatic impairment according to Child-Pugh Classification B or C.
• History of cataract surgery within 6 months prior to study treatment and participant is not anticipated to have cataract surgery during the study treatment period (as assessed by ophthalmological exam at baseline).
• Evidence of (as assessed by ophthalmological exam at baseline) uveitis, neovascular age related macular degeneration, retinal vein or artery occlusion and/or macular edema; no evidence of moderate or worsening diabetic retinopathy, retinal vascular disease or glaucoma (including participants with history of developing increased intraocular pressure after corticosteroid treatment) per clinical discretion of the consulting eye specialist.
• Peripheral neuropathy Grade >= 2 or Grade 1 with pain.
• Receipt of one of the following:

• Corticosteroids at a dose equivalent to > 4 mg daily of dexamethasone or a single dose of > 40 mg of dexamethasone within 2 weeks prior to first dose.
• Monoclonal antibodies used for multiple myeloma treatment within 4 weeks prior to first dose of study treatment.
• Any other systemic therapies used for multiple myeloma treatment within 5 half-lives or 2 weeks prior to first dose, whichever is longer (or 2 weeks if half-life is unknown).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Duplicate_Emory University, Winship Cancer Institute /ID# 222922

Atlanta, Georgia, United States

Norton Healthcare Pavilion /ID# 222918

Louisville, Kentucky, United States

Dana-Farber Cancer Institute /ID# 222174

Boston, Massachusetts, United States

Duke University Medical Center /ID# 222166

Durham, North Carolina, United States

University of Texas Southwestern Medical Center /ID# 223811

Dallas, Texas, United States

Institut Paoli-Calmettes /ID# 222307

Marseille, Bouches-du-Rhone, France

CHRU Lille - Hopital Claude Huriez /ID# 222302

Lille, Nord, France

CHU de Nantes, Hotel Dieu -HME /ID# 222303

Nantes, Pays de la Loire Region, France

HCL - Hopital Lyon Sud /ID# 222304

Pierre-Bénite, Rhone, France

Institut Gustave Roussy /ID# 223951

Villejuif, Val-de-Marne, France

Duplicate_Universitaetsklinikum Muenster /ID# 222504

Münster, North Rhine-Westphalia, Germany

Duplicate_Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz /ID# 222372

Mainz, Rhineland-Palatinate, Germany

Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 223014

Berlin, , Germany

Universitaetsklinikum Hamburg-Eppendorf /ID# 222258

Hamburg, , Germany

Duplicate_Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Universita /ID# 223224

Rome, Lazio, Italy

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 223839

Meldola, Reggio Emilia, Italy

Nagoya City University Hospital /ID# 222408

Nagoya, Aichi-ken, Japan

National Cancer Center Hospital East /ID# 239436

Kashiwa-shi, Chiba, Japan

Hospital Duran i Reynals /ID# 222329

L'Hospitalet de Llobregat, Barcelona, Spain

Countries

United States; France; Germany; Italy; Japan; Spain

Other Identifiers

2020-001983-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M20-258

Identifier Type: -

Identifier Source: org_study_id