A First In Human Study of the MCL-1 Inhibitor, ABBV-467
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 8
- Locations
- 24
- Primary Endpoint
- Number of Participants with Adverse Events
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Part A: ABBV-467 Dose Escalation
ABBV-467 administered by intravenous (IV) infusion at various doses until a recommended phase 2 dose is determined.
Intervention: ABBV-467 (Drug)
Part B: ABBV-467 Dose Expansion
ABBV-467 administered by intravenous (IV) infusion at recommended phase 2 dose as identified in Part A.
Intervention: ABBV-467 (Drug)
Outcomes
Primary Outcomes
Number of Participants with Adverse Events
Time Frame: Up to approximately 24 months after first dose of study drug
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.
Change in Vital Signs
Time Frame: Baseline (Week 0) through approximately 24 months after first dose of study drug
Change in vital signs like systolic and diastolic blood pressure will be assessed.
Change in Electrocardiogram (ECG)
Time Frame: Baseline (Week 0) through approximately 24 months after first dose of study drug
12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
Change in Cardiac Enzyme Levels
Time Frame: Baseline (Week 0) through approximately 24 months after first dose of study drug
Change in cardiac enzyme levels will be recorded.
Incidence of Abnormal Clinical Laboratory Test Results
Time Frame: Baseline (Week 0) through approximately 24 months after first dose of study drug
Number of participants with incidence of abnormal clinical laboratory test results like hematology will be assessed.
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Up to approximately Day 197
Maximum Plasma Concentration (Cmax) of ABBV-467.
Terminal Phase Elimination Half-life (t1/2)
Time Frame: Up to approximately Day 197
Terminal phase elimination half-life (t1/2) of ABBV-467
Area Under the Plasma Concentration-Time Curve (AUCt)
Time Frame: Up to approximately Day 197
AUC from time 0 to time of last measurable concentration of ABBV-467.
Area Under the Plasma Concentration-Time Curve (AUC0-infinity)
Time Frame: Up to approximately Day 197
AUC from time 0 to infinity of ABBV-467.
Clearance of ABBV-467
Time Frame: Up to approximately Day 197
Clearance of ABBV-467.
Secondary Outcomes
- 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)