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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04178902
• Other study ID #: M19-025
• Secondary ID: 2018-003744-24
• Status: Terminated
• Phase: Phase 1
• Start date: May 19, 2020
• Est. completion date: April 16, 2021

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: April 16, 2021
• Est. primary completion date: April 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Multiple Myeloma
• Multiple Myeloma (MM)
• Neoplasms, Plasma Cell

Intervention

Drug:
• ABBV-467
Intravenous (IV) Infusion

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 223354	Adelaide	South Australia
Australia	St Vincent's Hospital Melbourne /ID# 222066	Fitzroy	Victoria
Australia	Alfred Health /ID# 214665	Melbourne	Victoria
Australia	Perth Blood Institute Ltd /ID# 226650	Nedlands	Western Australia
Australia	Royal Perth Hospital /ID# 225498	Perth	Western Australia
France	Hopital Henri Mondor /ID# 214588	Creteil
France	CHU de Nantes, Hotel Dieu -HME /ID# 215480	Nantes	Pays-de-la-Loire
Israel	Sheba Medical Center /ID# 214065	Ramat Gan	Tel-Aviv
Japan	National Cancer Center Hospital /ID# 214801	Chuo-ku	Tokyo
Japan	Kyushu University Hospital /ID# 220800	Fukuoka-shi	Fukuoka
Japan	National Cancer Center Hospital East /ID# 214697	Kashiwa-shi	Chiba
Japan	Nagoya City University Hospital /ID# 214696	Nagoya shi	Aichi
Spain	Hospital Universitario Vall d'Hebron /ID# 214690	Barcelona
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 214739	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 214672	Madrid
Spain	Hospital Universitario Virgen de la Victoria /ID# 214756	Malaga
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 217170	Pamplona	Navarra, Comunidad
Taiwan	China Medical University Hosp /ID# 209323	Taichung City
Taiwan	National Taiwan University Hospital /ID# 209322	Taipei City	Taipei
United States	City of Hope /ID# 209786	Duarte	California
United States	Prisma Health Cancer Institute-Faris Road /ID# 219076	Greenville	South Carolina
United States	Hackensack Univ Med Ctr /ID# 221035	Hackensack	New Jersey
United States	Lifespan Cancer Institute at Rhode Island Hospital /ID# 215418	Providence	Rhode Island
United States	University of Arizona Cancer Center - North Campus /ID# 219102	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Japan,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Maximum Observed Plasma Concentration (Cmax)	Maximum Plasma Concentration (Cmax) of ABBV-467.	Up to approximately Day 197
Primary	Terminal Phase Elimination Half-life (t1/2)	Terminal phase elimination half-life (t1/2) of ABBV-467	Up to approximately Day 197
Primary	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
Primary	Area Under the Plasma Concentration-Time Curve (AUC0-infinity)	AUC from time 0 to infinity of ABBV-467.	Up to approximately Day 197
Primary	Clearance of ABBV-467	Clearance of ABBV-467.	Up to approximately Day 197
Secondary	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
Secondary	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
Secondary	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