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

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

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

Conditions
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Multiple Myeloma (MM), Cancer

Intervention / Treatment
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* Drug: ABBV-467


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma (MM), Relapse/Refractory, Cancer, ABBV-467