Trial Outcomes & Findings for A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML) (NCT NCT05028751)

A total of 24 participants were enrolled at sites in the United States and Spain.

A total of 35 participants were screened, of whom 24 participants were enrolled and received study treatment.

A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)

A TEAE was any unfavorable or unintended sign, symptom, laboratory abnormality or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered causally related to the study drug or not that started after the first dose of the earliest study drug through the lesser of non-protocol anti-leukemic therapy initiation or end of treatment visit. A serious TEAE was defined as any TEAE that: * Resulted in death. * Was life-threatening. * Required or prolonged a pre-existing hospitalization. * Resulted in disability/incapacity. * Was a congenital anomaly/birth defect. * Was considered a significant medical event by the investigator. TEAEs were graded for severity based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as follows: * Grade 1 - Mild. * Grade 2 - Moderate. * Grade 3 - Severe. * Grade 4 - Life-threatening. * Grade 5 - Death related to adverse event (AE).

A DLT was defined as any of the following occurring within the DLT assessment period: * A nonhematologic toxicity of Grade ≥ 3 that was at least possibly related to LANRA (with noted exceptions). * Any toxicity that resulted in administration of \< 80% of the cumulative, Cycle 1 dose for either LANRA or gilteritinib. * Grade 4 neutropenia or thrombocytopenia lasting \> 28 days after treatment onset that was not attributed to active acute myeloid leukemia (AML) and was at least possibly related to LANRA. * Any toxicity that resulted in reduction in the dose of LANRA in Cycle 1. DLTs were graded for severity based on the NCI-CTCAE version 5.0 as follows: * Grade 3 - Severe. * Grade 4 - Life-threatening.

The MTD/RP2D was defined as the highest dose with either 0 of 3 or no more than 1 of 6 patients with LANRA-related DLTs. All decisions regarding dose escalation including declaration of the MTD/RP2D were made by the dose-escalation committee (DEC).

Cmax was derived from plasma concentrations of LANRA using standard non-compartmental methods and actual sample times.

Tmax was derived from plasma concentrations of LANRA using standard non-compartmental methods and actual sample times.

AUC0-last was derived from plasma concentrations of LANRA using standard non-compartmental methods and actual sample times.

Cmax was derived from plasma concentrations of gilteritinib using standard non-compartmental methods and actual sample times.

Tmax was derived from plasma concentrations of gilteritinib using standard non-compartmental methods and actual sample times.

AUC0-last was derived from plasma concentrations of gilteritinib using standard non-compartmental methods and actual sample times.

Percentage of participants with cCR included CR and CR with partial hematologic recovery (CRh). CR required all of the following, per ELN 2017 criteria: * Bone marrow blasts \< 5 %. * Absence of circulating blasts and blasts with Auer rods. * Absence of extramedullary disease (ie, leukemia outside of bone marrow confirmed by biopsy). * Absolute neutrophil count \> 1.0 x 10\^9/L (1,000/μL). * Platelet count \>100 x 10\^9/L (100,000/μL). CRh required all aforementioned CR criteria except for the below: * Absolute neutrophil count \> 0.5 x 10\^9/L (500/μL) and/or; * Platelet count \> 50 x 10\^9/L (50,000/μL).

DOR was defined as the time from first qualifying response (CR/CRh) until relapse or death from any cause, as assessed by study investigators. CR required all of the following: * Bone marrow blasts \< 5 %. * Absence of circulating blasts and blasts with Auer rods. * Absence of extramedullary disease (ie, leukemia outside of bone marrow confirmed by biopsy). * Absolute neutrophil count \> 1.0 x 10\^9/L (1,000/μL). * Platelet count \>100 x 10\^9/L (100,000/μL). CRh required all aforementioned CR criteria except for the below: * Absolute neutrophil count \> 0.5 x 10\^9/L (500/μL) and/or; * Platelet count \> 50 x 10\^9/L (50,000/μL). Relapse was defined as the reappearance of circulating blasts or ≥ 5% blasts in the bone marrow not attributable to any other cause or reappearance of cytologically or biopsy documented extramedullary disease.

EFS was defined as the time from treatment onset until treatment failure (ie, failure to achieve CR/CRh, relapse from CR/CRh, or death from any cause). CR required all of the following: * Bone marrow blasts \< 5 %. * Absence of circulating blasts and blasts with Auer rods. * Absence of extramedullary disease (ie, leukemia outside of bone marrow confirmed by biopsy). * Absolute neutrophil count \> 1.0 x 10\^9/L (1,000/μL). * Platelet count \>100 x 10\^9/L (100,000/μL). CRh required all aforementioned CR criteria except for the below: * Absolute neutrophil count \> 0.5 x 10\^9/L (500/μL) and/or; * Platelet count \> 50 x 10\^9/L (50,000/μL). Relapse was defined as the reappearance of circulating blasts or ≥ 5% blasts in the bone marrow not attributable to any other cause or reappearance of cytologically or biopsy documented extramedullary disease.

Overall survival was defined as the time from enrollment until death from any cause. Overall survival was estimated using Kaplan-Meier methodology.