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

NCT04570631 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M20-2582020-001983-26
• Study Type: interventional
• Target: 4
• Locations: 6 countries
• Sites: 19

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

Keywords

Multiple Myeloma (MM); Relapsed/Refractory Multiple Myeloma; Eftozanermin Alfa; ABBV-621; Bortezomib; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) of Eftozanermin Alfa in Combination With Bortezomib and Dexamethasone (Safety Lead-In Arm)

  RP2D of eftozanermin alfa in combination with bortezomib and dexamethasone will be determined.

  Up to approximately 3 weeks after the first dose of study drug

• Objective Response Rate (ORR) (Dose Expansion Arm)

  ORR is defined as percentage of participants with a response of partial response (PR) or better per International Myeloma Working Group (IMWG) criteria.

  Up to approximately 44 weeks after the first dose of study drug

Secondary Outcomes (11)

• Rate of Very Good Partial Response (VGPR) or Better per IMWG Criteria

  Up to approximately 44 weeks after the first dose of study drug

• Duration of Response (DOR) for ORR

  Up to approximately 44 weeks after the first dose of study drug

• Duration of Response (DOR) for VGPR or Better

  Up to approximately 44 weeks after the first dose of study drug

• Number of Participants With Dose-Limiting Toxicities (DLTs)

  Up to approximately 3 weeks after the first dose of study drug

• Number of Participants With Adverse Events (AEs)

  Up to approximately 44 weeks after the first dose of study drug

Study Arms (2)

Safety Lead-in

EXPERIMENTAL

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

Drug: Eftozanermin alfa; Drug: Bortezomib; Drug: Dexamethasone

Dose Expansion

EXPERIMENTAL

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

Drug: Eftozanermin alfa; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Eftozanermin alfa DRUG

Intravenous (IV) infusion

Also known as: ABBV-621

Dose Expansion; Safety Lead-in

Bortezomib DRUG

Intravenous (IV) or Subcutaneous (SC) injection

Dose Expansion; Safety Lead-in

Dexamethasone DRUG

Oral Tablet

Dose Expansion; Safety Lead-in

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AbbVie: lead

Study Sites (19)

Duplicate_Emory University, Winship Cancer Institute /ID# 222922

Atlanta, Georgia, 30322, United States

Location

Norton Healthcare Pavilion /ID# 222918

Louisville, Kentucky, 40202, United States

Location

Dana-Farber Cancer Institute /ID# 222174

Boston, Massachusetts, 02215, United States

Location

Duke University Medical Center /ID# 222166

Durham, North Carolina, 27710, United States

Location

University of Texas Southwestern Medical Center /ID# 223811

Dallas, Texas, 75390-7208, United States

Location

Institut Paoli-Calmettes /ID# 222307

Marseille, Bouches-du-Rhone, 13009, France

Location

CHRU Lille - Hopital Claude Huriez /ID# 222302

Lille, Nord, 59037, France

Location

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

Nantes, Pays de la Loire Region, 44000, France

Location

HCL - Hopital Lyon Sud /ID# 222304

Pierre-Bénite, Rhone, 69495, France

Location

Institut Gustave Roussy /ID# 223951

Villejuif, Val-de-Marne, 94805, France

Location

Duplicate_Universitaetsklinikum Muenster /ID# 222504

Münster, North Rhine-Westphalia, 48149, Germany

Location

Duplicate_Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz /ID# 222372

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 223014

Berlin, 12203, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf /ID# 222258

Hamburg, 20246, Germany

Location

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

Rome, Lazio, 00168, Italy

Location

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

Meldola, Reggio Emilia, 47014, Italy

Location

Nagoya City University Hospital /ID# 222408

Nagoya, Aichi-ken, 467-8602, Japan

Location

National Cancer Center Hospital East /ID# 239436

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Hospital Duran i Reynals /ID# 222329

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: September 30, 2020
• Study Start: November 5, 2020
• Primary Completion: May 5, 2025
• Study Completion: May 5, 2025
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); DE (4); JP (2); ES (1); US (5); IT (2)