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

NCT04178902 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M19-0252018-003744-24
• Study Type: interventional
• Target: 8
• Locations: 7 countries
• Sites: 24

Brief Summary

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

Conditions

Multiple Myeloma (MM); Cancer

Keywords

Multiple Myeloma (MM); Relapse/Refractory; Cancer; ABBV-467

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (3)

• Overall Response Rate (ORR)

  Up to approximately 24 months after first dose of study drug

• Clinical Benefit Rate (CBR)

  Up to approximately 24 months after first dose of study drug

• Duration of Response (DOR)

  Up to approximately 24 months after first dose of study drug

Study Arms (2)

Part A: ABBV-467 Dose Escalation

EXPERIMENTAL

ABBV-467 administered by intravenous (IV) infusion at various doses until a recommended phase 2 dose is determined.

Drug: ABBV-467

Part B: ABBV-467 Dose Expansion

EXPERIMENTAL

ABBV-467 administered by intravenous (IV) infusion at recommended phase 2 dose as identified in Part A.

Drug: ABBV-467

Interventions

ABBV-467 DRUG

Intravenous (IV) Infusion

Part A: ABBV-467 Dose Escalation; Part B: ABBV-467 Dose Expansion

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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (24)

University of Arizona Cancer Center - North Campus /ID# 219102

Tucson, Arizona, 85719-1478, United States

Location

City of Hope /ID# 209786

Duarte, California, 91010, United States

Location

Hackensack Univ Med Ctr /ID# 221035

Hackensack, New Jersey, 07601, United States

Location

Lifespan Cancer Institute at Rhode Island Hospital /ID# 215418

Providence, Rhode Island, 02903-4923, United States

Location

Prisma Health Cancer Institute-Faris Road /ID# 219076

Greenville, South Carolina, 29605-4255, United States

Location

Royal Adelaide Hospital /ID# 223354

Adelaide, South Australia, 5000, Australia

Location

St Vincent's Hospital Melbourne /ID# 222066

Fitzroy, Victoria, 3065, Australia

Location

Alfred Health /ID# 214665

Melbourne, Victoria, 3004, Australia

Location

Perth Blood Institute Ltd /ID# 226650

Nedlands, Western Australia, 6009, Australia

Location

Royal Perth Hospital /ID# 225498

Perth, Western Australia, 6000, Australia

Location

CHU de Nantes, Hotel Dieu -HME /ID# 215480

Nantes, Pays de la Loire Region, 44000, France

Location

Hopital Henri Mondor /ID# 214588

Créteil, 94000, France

Location

Sheba Medical Center /ID# 214065

Ramat Gan, Tel Aviv, 5239424, Israel

Location

Nagoya City University Hospital /ID# 214696

Nagoya, Aichi-ken, 467-8602, Japan

Location

National Cancer Center Hospital East /ID# 214697

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Kyushu University Hospital /ID# 220800

Fukuoka, Fukuoka, 812-8582, Japan

Location

National Cancer Center Hospital /ID# 214801

Chuo-ku, Tokyo, 104-0045, Japan

Location

CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 217170

Pamplona, Navarra, Comunidad, 31008, Spain

Location

Hospital Universitario Vall d'Hebron /ID# 214690

Barcelona, 08035, Spain

Location

CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 214739

Madrid, 28027, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 214672

Madrid, 28040, Spain

Location

Hospital Universitario Virgen de la Victoria /ID# 214756

Málaga, 29010, Spain

Location

National Taiwan University Hospital /ID# 209322

Taipei City, Taipei, 10002, Taiwan

Location

China Medical University Hosp /ID# 209323

Taichung, 40447, Taiwan

Location

Related Publications (1)

• Yuda J, Will C, Phillips DC, Abraham L, Alvey C, Avigdor A, Buck W, Besenhofer L, Boghaert E, Cheng D, Cojocari D, Doyle K, Hansen TM, Huang K, Johnson EF, Judd AS, Judge RA, Kalvass JC, Kunzer A, Lam LT, Li R, Martin RL, Mastracchio A, Mitten M, Petrich A, Wang J, Ward JE, Zhang H, Wang X, Wolff JE, Bell-McGuinn KM, Souers AJ. Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients. Commun Med (Lond). 2023 Oct 25;3(1):154. doi: 10.1038/s43856-023-00380-z.

  PMID: 37880389 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: November 25, 2019
• First Posted: November 26, 2019
• Study Start: May 19, 2020
• Primary Completion: April 16, 2021
• Study Completion: April 16, 2021
• Last Updated: July 26, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); JP (4); FR (2); IL (1); TW (2); ES (5); US (5)