A Study of the Safety and Tolerability of ABBV-467 in Adult Participants With Relapsed/Refractory (R/R) Multiple Myeloma

A First In Human Study of the MCL-1 Inhibitor, ABBV-467

This first-in-human study will evaluate the safety and tolerability of ABBV-467 in adult participants with relapsed/refractory multiple myeloma (MM).

Study Overview

• Status: Terminated
• Conditions: Cancer; Multiple Myeloma (MM)
• Intervention / Treatment: Drug: ABBV-467

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital /ID# 223354
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne /ID# 222066
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health /ID# 214665
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perth Blood Institute Ltd /ID# 226650
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital /ID# 225498
• France
  • Creteil, France, 94000
    • Hopital Henri Mondor /ID# 214588
  • Pays-de-la-Loire
    • Nantes, Pays-de-la-Loire, France, 44000
      • CHU de Nantes, Hotel Dieu -HME /ID# 215480
• Israel
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5239424
      • Sheba Medical Center /ID# 214065
• Japan
  • Aichi
    • Nagoya shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital /ID# 214696
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 214697
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 220800
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 214801
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 214690
  • Madrid, Spain, 28027
    • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 214739
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 214672
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria /ID# 214756
  • Navarra, Comunidad
    • Pamplona, Navarra, Comunidad, Spain, 31008
      • CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 217170
• Taiwan
  • Taichung City, Taiwan, 40447
    • China Medical University Hosp /ID# 209323
  • Taipei
    • Taipei City, Taipei, Taiwan, 10002
      • National Taiwan University Hospital /ID# 209322
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719-1478
      • University of Arizona Cancer Center - North Campus /ID# 219102
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 209786
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Med Ctr /ID# 221035
  • Rhode Island
    • Providence, Rhode Island, United States, 02903-4923
      • Lifespan Cancer Institute at Rhode Island Hospital /ID# 215418
  • South Carolina
    • Greenville, South Carolina, United States, 29605-4255
      • Prisma Health Cancer Institute-Faris Road /ID# 219076

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented diagnosis of multiple myeloma (MM).

• Measurable disease defined as at least 1 of the following:

  • Serum monoclonal protein >= 1g/dL.
  • Urine M-protein >= 200mg/24 hours.
  • Serum immunoglobulin free light chain (FLC) >= 10 mg/dL (100 mg/L), provided serum FLC ratio is abnormal.
• Relapsed after or are refractory or intolerant to all established MM therapies that are both known to provide clinical benefit and locally available.
• Received at least 3 prior lines of therapy including 1 or more immunomodulatory agents, 1 or more proteasome inhibitors, and 1 or more anti-CD38 monoclonal antibodies.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Adequate hematologic, renal and hepatic function as described in the protocol.
• Echocardiogram with ejection fraction >= 50% and no other clinically significant findings that would increase the participant's susceptibility to cardiac toxicity.

Exclusion Criteria:

• Prior exposure to any targeted myeloid cell leukemia-1 (MCL-1) inhibitor.
• Antineoplastic therapy (including any cytotoxic, targeted and/or investigational therapy; but not including corticosteroids), within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study drug and through the last dose of study drug.
• Autologous stem cell transplant within 90 days prior to start of study drug.
• Allogenic stem cell transplant within 180 days prior to start of study drug.
• History of acute or chronic pancreatitis.
• Significant unresolved liver disease.
• History of hepatitis B or human immunodeficiency virus (HIV) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: ABBV-467 Dose Escalation; ABBV-467 administered by intravenous (IV) infusion at various doses until a recommended phase 2 dose is determined.	Drug: ABBV-467; Intravenous (IV) Infusion
Experimental: Part B: ABBV-467 Dose Expansion; ABBV-467 administered by intravenous (IV) infusion at recommended phase 2 dose as identified in Part A.	Drug: ABBV-467; Intravenous (IV) Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator will assess the relationship of each event to the use of study drug as being of reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug.	Up to approximately 24 months after first dose of study drug
Change in Vital Signs	Change in vital signs like systolic and diastolic blood pressure will be assessed.	Baseline (Week 0) through approximately 24 months after first dose of study drug
Change in Electrocardiogram (ECG)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.	Baseline (Week 0) through approximately 24 months after first dose of study drug
Change in Cardiac Enzyme Levels	Change in cardiac enzyme levels will be recorded.	Baseline (Week 0) through approximately 24 months after first dose of study drug
Incidence of Abnormal Clinical Laboratory Test Results	Number of participants with incidence of abnormal clinical laboratory test results like hematology will be assessed.	Baseline (Week 0) through approximately 24 months after first dose of study drug
Maximum Observed Plasma Concentration (Cmax)	Maximum Plasma Concentration (Cmax) of ABBV-467.	Up to approximately Day 197
Terminal Phase Elimination Half-life (t1/2)	Terminal phase elimination half-life (t1/2) of ABBV-467	Up to approximately Day 197
Area Under the Plasma Concentration-Time Curve (AUCt)	AUC from time 0 to time of last measurable concentration of ABBV-467.	Up to approximately Day 197
Area Under the Plasma Concentration-Time Curve (AUC0-infinity)	AUC from time 0 to infinity of ABBV-467.	Up to approximately Day 197
Clearance of ABBV-467	Clearance of ABBV-467.	Up to approximately Day 197

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR evaluated per adapted International Myeloma Working Group (IMWG) criteria and defined as partial response (PR) + very good partial response (VGPR) + complete remission (CR) + stringent complete response (sCR).	Up to approximately 24 months after first dose of study drug
Clinical Benefit Rate (CBR)	CBR evaluated per adapted International Myeloma Working Group (IMWG) criteria and is defined as minimal response (MR) + PR + VGPR + CR + sCR.	Up to approximately 24 months after first dose of study drug
Duration of Response (DOR)	DOR is defined as the time between date of first response and the first occurrence of progression or death from any cause, whichever comes first.	Up to approximately 24 months after first dose of study drug

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2020
• Primary Completion (Actual): April 16, 2021
• Study Completion (Actual): April 16, 2021

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Cancer; Multiple Myeloma (MM); Relapse/Refractory; ABBV-467
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: M19-025; 2018-003744-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes