Eganelisib + Venetoclax and Azacitidine (GAVEL)

PI3K-gamma inhibitor, capsule taken orally per protocol.

Demethylating Agent, single use vial, via subcutaneous (under the skin) injection or intravenous (into the vein) infusion per standard of care.

This phase 1 clinical trial is to evaluate the safety and preliminary efficacy of adding the PI3K-gamma inhibitor, eganelisib, to a standard of care treatment option with combination venetoclax and azacitidine in participants with acute myeloid leukemia (AML). The dose-escalation portion of the trial will aim to establish the maximum tolerated dose of the drug, eganelisib, for the recommended phase 2 dose.

This study is to evaluate the safety and preliminary efficacy of adding the PI3K-gamma inhibitor, eganelisib, to a standard of care treatment option with combination venetoclax and azacitidine in participants with acute myeloid leukemia (AML). The names of the study drugs involved in this research study are: * Venetoclax (a type of BCL-2 inhibitor) * Azacitidine (a type of Demethylating Agent) * Eganelisib (a type of PI3K-gamma inhibitor)

Live record on ClinicalTrials.gov →

• Group A: Relapsed or Refractory: Subjects with relapsed or refractory AML or relapsed/refractory AML, who are not recommended for any approved targeted therapy must meet any one of the following criteria: (1) morphologic relapse (at least 5% blasts), or (2) refractory to intensive chemotherapy (at least one cycle of cytarabine and anthracycline-based intensive regimen) or at least 2 cycles of prior HMA/venetoclax-based therapy (without CR/CRh/CRi). No limit to prior lines of AML therapy. OR
• (Expansion only) Group B: Untreated AML with ELN 2022 adverse risk disease: Subjects with newly diagnosed or previously untreated AML must be ineligible for intensive chemotherapy based on Ferrara criteria (age ≥75 years or presence of co- morbidity).
• Evidence of marrow involved AML.
• Age 18-90 years. Because no dosing or adverse event data are currently available on the use of eganelisib in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group performance status ≤ 3 if 18 to 74 years of age or ECOG 0-2 if ≥ 75 years of age.

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.