Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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Acute myeloid leukemia (AML) is the second most common type of leukemia diagnosed in adults and children, but most cases occur in adults. This study is to evaluate how safe ABBV-787 is and how it moves within the body in adult participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). Adverse events and maximum tolerated dose (MTD) of ABBV-787 will be assessed. ABBV-787 is an investigational drug being developed for the treatment of AML. Participants will receive ABBV-787 in escalating doses until the maximum tolerated dose (MTD) is determined. Approximately 60 adult participants with a diagnosis of AML will be enrolled worldwide. Participants will receive intravenous (IV) infusions of ABBV-787 during the approximately 3 year duration a participant is followed. There may be 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 the treatment will be checked by medical assessments, blood tests and checking for side effects.

Official Title
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A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-787 in Adult Subjects With Acute Myeloid Leukemia (AML)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: ABBV-787


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Laboratory Criteria matching those outlined in the protocol. QT interval corrected for heart rate (QTc) <= 470 msec using Fridericia's correction, and no other clinically significant cardiac abnormalities. Documented diagnosis of non-promyelocytic acute myeloid leukemia (AML), per 2022 European Leukemia Net (ELN) criteria. Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) who have been treated with up to 3 prior lines of therapy and are refractory to or intolerant of all established AML therapies that are known to clearly provide clinical benefit at the judgement of the investigator. Must have a white blood cell (WBC) count < 25 × 10^9 /L prior to initiation of study drug (Note: Hydroxyurea or leukapheresis is permitted to meet this criterion and for use through Cycle 3 to control for hyperleukocytosis.). Exclusion Criteria: Have received a CD33-targeting therapy within 3 months prior to the first dose of ABBV-787. Stem cell transplant within 3 months prior to first dose of study drug. Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-787. History of documented pneumonitis that required treatment with systemic steroids within the last 6 months, nor any evidence of active pneumonitis. Unresolved toxicity of Grade >= 2 from prior anticancer therapy, or to levels dictated in the eligibility criteria, with the exception of alopecia. Known active severe or poorly controlled acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-787<br>Participants will receive increasing doses of ABBV-787 until the maximum tolerated dose (MTD) during the 3 year treatment period. | Drug: ABBV-787<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 (AE) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | Up to Approximately 3 Years | 
| Maximum Tolerated Dose (MTD) Based on Dose-Limiting Toxicities (DLT) | DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications. | Up to approximately 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve (AUC) of ABBV-787 | AUC of ABBV-787. | Up to Approximately 1 Year | 
| Maximum Observed Concentration (Cmax) of ABBV-787 | Cmax of ABBV-787. | Up to Approximately 1 Year | 
| Time to Cmax (Tmax) of ABBV-787 | Tmax of ABBV-787. | Up to Approximately 1 Year | 
| Half-life (t1/2) of ABBV-787 | t1/2 of ABBV-787. | Up to Approximately 1 Year | 
| Total Antibody Concentration | Total antibody concentration | Up to Approximately 1 Year | 
| Plasma Concentrations of Unconjugated Bromodomain and Extra-terminal Domain (BET) Degrader Payload | Plasma concentrations of unconjugated BET degrader payload. | Up to Approximately 1 Year | 
| Antidrug Antibody (ADA) | Incidence and concentration of anti-drug antibodies. | Up to Approximately 1 Year | 
| Neutralizing Antibody (nAb) | Incidence and concentration of neutralizing antibodies. | Up to Approximately 1 Year | 
| Percentage of Participants Achieving Complete Remission (CR) | CR is assessed by the European Leukemia Net (ELN). ELN defines refractory disease as the inability to attain complete remission (CR) or CR with incomplete hematologic recovery (CRi) after two courses of intensive induction treatment. | Up to Approximately 1 Year | 
| Rate of Participants Achieving CR with partial hematologic recovery (CRh) | Percentage of participants achieving CRh per ELN 2022. | Up to Approximately 1 Year | 
| Rate of Participants Achieving CR with incomplete hematologic recovery (CRi) | Percentage of participants achieving CRi per ELN 2022. | Up to Approximately 1 Year | 
| Rate of Participants Achieving Composite CR (CR, CRh, or CRi) | Composite CR is defined as the percentage of participants with composite CR per ELN 2022. | Up to Approximately 1 Year | 
| Rate of Participants Achieving Partial Remission (PR) | PR is defined as the percentage of participants with PR per ELN 2022. | Up to Approximately 1 Year | 
| Duration of Response (DOR) | DOR is defined for participants with CR, CRh, CRi, or PR as the time from the participant's initial response of CR, CRh, CRi, or PR per investigator review according to ELN 2022 criteria to disease progression or death of any cause, whichever occurs earlier. | Up to Approximately 1 Year | 
| Number of Participants proceeding to hematopoietic stem cell transplant (HSCT) | Number of participants proceeding to HSCT | Up to Approximately 3 Years | 
| Event-free Survival (EFS) | EFS is defined as the time from the date of the first study treatment to the date of treatment failure, or hematologic relapse from either CR, CRh, or CRi, or death from any cause, whichever occurs earlier. | Up to Approximately 3 Years | 
| Relapse free survival (RFS) | RFS is defined for participants achieving CR, CRh, or CRi as time from the date of achievement of remission (CR, CRh, or CRi) until the date of hematologic relapse or death from any cause. | Up to Approximately 3 Years | 
| Overall survival (OS) | OS is defined as time from first study treatment to death from any cause. | Up to Approximately 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, AML, ABBV-787