Clinical trial NCT04570631: 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
Official title: A Phase 1b, Open-Label Study of Eftozanermin Alfa (ABBV-621) in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma (MM)
Relapsed/Refractory Multiple Myeloma
Eftozanermin Alfa
ABBV-621
Bortezomib
Dexamethasone
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-09-30
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D) of Eftozanermin Alfa in Combination With Bortezomib and Dexamethasone (Safety Lead-In Arm)
timeFrame: Up to approximately 3 weeks after the first dose of study drug
measure: Objective Response Rate (ORR) (Dose Expansion Arm)
timeFrame: Up to approximately 44 weeks after the first dose of study drug
Secondary outcomes:
measure: Rate of Very Good Partial Response (VGPR) or Better per IMWG Criteria
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Duration of Response (DOR) for ORR
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Duration of Response (DOR) for VGPR or Better
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Up to approximately 3 weeks after the first dose of study drug
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Change in Vital Sign Measurements
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Electrocardiogram (ECG)
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Number of Participants With Abnormal Clinical Laboratory Test Results
timeFrame: Up to approximately 44 weeks after the first dose of study drug
measure: Trough Concentration (Ctrough) of Eftozanermin Alfa
timeFrame: Up to Day 106
measure: Maximum Serum Concentration (Cmax) of Eftozanermin Alfa
timeFrame: Up to Day 8
measure: Antidrug Antibody (ADA)/Neutralizing Antibody (Nab) Assay
timeFrame: Up to approximately 44 weeks after the first dose of study drug
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Duplicate_Emory University, Winship Cancer Institute /ID# 222922
state: Georgia
city: Louisville
country: United States
facility: Norton Healthcare Pavilion /ID# 222918
state: Kentucky
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 222174
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center /ID# 222166
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 223811
state: Texas
city: Marseille
country: France
facility: Institut Paoli-Calmettes /ID# 222307
state: Bouches-du-Rhone
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 222302
state: Nord
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu -HME /ID# 222303
state: Pays-de-la-Loire
city: Pierre Benite CEDEX
country: France
facility: HCL - Hopital Lyon Sud /ID# 222304
state: Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 223951
state: Val-de-Marne
city: Muenster
country: Germany
facility: Duplicate_Universitaetsklinikum Muenster /ID# 222504
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Duplicate_Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz /ID# 222372
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Charite Universitaetsklinikum Berlin - Campus Benjamin Franklin /ID# 223014
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf /ID# 222258
city: Rome
country: Italy
facility: Duplicate_Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Universita /ID# 223224
state: Lazio
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 223839
state: Reggio Emilia
city: Nagoya shi
country: Japan
facility: Nagoya City University Hospital /ID# 222408
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 239436
state: Chiba
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals /ID# 222329
state: Barcelona
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: