A Study to Determine Safety, Tolerability, Pharmacokinetics, and Recommended Phase 2 Dose (RP2D) of Intravenous ABBV-184 in Adult Participants With Previously Treated Cancers

Study Overview
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Brief Summary
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Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. This study focuses on two types of cancers: Acute Myeloid Leukemia (AML) and Non-Small Cell Lung Cancer (NSCLC). AML (blood cancer) is cancer of the white blood cells (WBC). NSCLC (solid tumor) is a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to determine recommended phase 2 dose (RP2D) and to see if the study drug is safe and able to treat patients who have AML and NSCLC. ABBV-184 is an investigational drug being developed for treatment of cancer. The study has two arms and two phases: AML arm and NSCLC arm; dose escalation and dose expansion phase. Adult participants with diagnosis of AML or NSCLC will be enrolled. In dose escalation phase, around 36 participants will be enrolled in each arm. In dose expansion phase, around 20 participants will be enrolled in each arm. The study will be conducted in approximately 50 sites across 10 countries. Participants will receive weight based intravenous (IV) infusion of ABBV-184 once a week. At the beginning of the study, visits will occur daily during hospitalization followed by less frequently over time. There will be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood tests, checking for side effects, and questionnaires.

Official Title
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A Phase 1 First in Human, Multicenter, Open-Label Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics, and RP2D of ABBV-184 in Subjects With Previously Treated Cancers

Conditions
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Acute Myeloid Leukemia (AML), Non Small Cell Lung Cancer, Cancer

Intervention / Treatment
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* Drug: ABBV-184


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute myeloid leukemia (AML) or non-small cell lung cancer (NSCLC). Participants must consent to hospitalization for at least 72 hours following the first two doses of ABBV-184 in Cycle 1. Participants must have Human Leukocyte Antigen-A2 (HLA-A2) restricted genotype. Participants must be HLA-A2:01 positive in at least one allele tested with a high-resolution HLA genotyping assay performed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA)-certified or equivalent laboratory. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Laboratory values and cardiac function must meet the protocol specifications. Exclusion Criteria: For AML participants: Presence or history of extramedullary disease are ineligible, participants with a diagnosis of acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia are not eligible. For NSCLC participants: Tumors with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) gene rearrangements are not eligible. Active/uncontrolled central nervous system (CNS) leukemia/lung cancer are not eligible for the study. History of inflammatory bowel disease, interstitial lung disease (pneumonitis), myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis, solid organ transplantation, active autoimmune disease (with exceptions of vitiligo, Type I diabetes mellitus, hypothyroidism, and psoriasis), primary immunodeficiency. History of clinical diagnosis of tuberculosis or major immunologic reaction to any immunoglobulin G (IgG)-containing agent are not eligible. Previously received anti-cancer treatment with an agent that targets the immune system by engaging cluster of differentiation 3 (CD3) are not eligible.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: Participants With AML<br>Participants with relapsed or refractory (R/R) AML will receive escalating doses of ABBV-184 | Drug: ABBV-184<br>* Intravenous (IV) infusion<br>|
| Experimental: Dose Escalation: Participants With NSCLC<br>Participants with relapsed or refractory (R/R) NSCLC will receive escalating doses of ABBV-184 | Drug: ABBV-184<br>* Intravenous (IV) infusion<br>|
| Experimental: Dose Expansion: Participants With AML<br>Participants with R/R AML will receive ABBV-184 at recommended Phase 2 dose (RP2D) determined in dose escalation phase for AML | Drug: ABBV-184<br>* Intravenous (IV) infusion<br>|
| Experimental: Dose Expansion: Participants With NSCLC<br>Participants with R/R NSCLC will receive ABBV-184 at RP2D determined in dose escalation phase for NSCLC | Drug: ABBV-184<br>* Intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase) | The RP2D of ABBV-184 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data. | Up to 1 Cycle after the last participant is enrolled in dose escalation phase (Approximately 2 years) | 
| Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh) Rate (Dose Expansion Phase in Participants With AML) | CR/CRh rate is assessed based on the Clopper-Pearson (exact) method. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Objective Response Rate (ORR) (Dose Expansion Phase in Participants With NSCLC) | ORR is defined as participants with confirmed complete or partial response (CR+PR) per RECIST, v1.1 | Up to 30 days after last participant complete study drug (Approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. 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 participant and may require medical or surgical intervention to prevent any of the outcomes listed above. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Laboratory Parameters | Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Vital Signs | Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Montreal Cognitive Assessment (MoCA) | The Montreal Cognitive Assessment (MoCA) is a one page 30-point written test that assesses cognitive function. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Echocardiogram | Number of participants with abnormal change from baseline in echocardiogram will be reported. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Electrocardiogram (ECG) | 12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Maximum Observed Serum Concentration (Cmax) of ABBV-184 | Maximum Serum Concentration (Cmax) of ABBV-184. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Time to Maximum Observed Serum Concentration (Tmax) | Time to Maximum Serum Concentration (Tmax) of ABBV-184. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Terminal Phase Elimination Rate Constant (β) for ABBV-184 | Terminal Phase Elimination Rate Constant (β) for ABBV-184. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Terminal Phase Elimination Half-life (t1/2) of ABBV-184 | Terminal Phase Elimination Half-life (t1/2) of ABBV-184. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Area Under the Serum Concentration-Time Curve of ABBV-184 | Area Under the Serum Concentration-Time Curve of ABBV-184. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Percentage of Participants With Anti-drug Antibodies (ADAs) | Percentage of Participants With Anti-drug Antibodies (ADAs) | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Duration of Response (DOR) (Dose Expansion Phase) | DOR is defined as the time between date of first response and the first occurrence of progression or death from any cause, whichever occurs first. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Progression-free Survival (PFS) (Dose Expansion Phase) | PFS will be defined as the time between the first dose of any study drug and the first occurrence of progression or death from any cause. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Relapse-Free Survival (RFS) (Dose Expansion Phase in Participants With AML) | RFS is defined as the time between date of first response and the first occurrence of progression or death from any cause, whichever occurs first. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Bone Marrow Blast Count (Dose Expansion Phase in Participants With AML) | Percentage of blast cells in bone marrow. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Change in Peripheral Blood Blast Count (Dose Expansion Phase in Participants With AML) | Percentage of blast cells in peripheral blood. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Objective Response Rate (ORR) (Dose Expansion Phase in Participants With AML) | ORR is defined as the proportion of participants with complete remission (CR), morphologic complete remission with incomplete blood count recovery (CRi), complete remission with partial hematologic recovery (CRh), complete response with incomplete platelet recovery (CRp), and partial remission (PR). | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Rate of Conversion to Transfusion Independence (Dose Expansion Phase in Participants With AML) | AML participants will be considered to have converted to transfusion independence if they receive no red blood cell transfusion, platelet transfusion, or growth factors for a 56-day window after beginning study treatment. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 
| Clinical Benefit Rate (CBR) (Dose Expansion Phase in Participants With NSCLC) | CBR is defined as the proportion of participants with a CR, PR, or stable disease (SD) for at least 6 weeks by RECIST 1.1 criteria. | Up to 30 days after last participant complete study drug (Approximately 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors Cancer, Acute Myeloid Leukemia (AML), Non Small Cell Lung Cancer (NSCLC), Blood Cancer, ABBV-184, Cancer