Neoplasms

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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Subjects with Advanced primary AML or MDS secondary to AML or AML-MR.

Seven dosing cohorts will be evaluated in the dose escalation phase: 20mg, 40mg,80mg,120mg, 160mg, 200mg, 240mg.Expansion is planned in three dose groups of 120mg, 160mg, and 200mg.

STI-8591

Jie Jin, Doctor

This is a first-in-human, dose-escalation and dose-expansion Phase I study to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of STI-8591 in subjects with advanced AML who have signed an informed consent form (ICF) and have been screened for enrollment in this study.

* Dose escalation phase: rapid titration and conventional 3+3 test design were used to evaluate the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and PK characteristics of STI-8591.
* Dose Expansion Phase: Evaluate the safety, preliminary efficacy and determine the recommended phase II dose (RP2D) of STI-8591 for the treatment of subjects with advanced AML under the conditions of reaching the expanded dose.

Dose escalation phase:Based on the preclinical trial data and with reference to the modified Fibonacci method, the dose escalation ratios are 100%, 100%, 50% and 6.7%, and the initial 5 dose groups for STI-8591 dose escalation are 40, 80, 160, 240 and 280 mg/day, respectively. Screened subjects will be entered into the 5 dose groups in order of succession from lowest to highest dose.This test dose increment will be performed using the rapid titration method and the traditional 3+3 test design.

Dose expansion phase:During dose escalation, for dose groups (except for ≥2 DLT dose groups) when the following dose signals suggesting initial efficacy are present.

1) CR, CRh or CRi in ≥1 subject in either dose group.2) Median decrease in FLT3 phosphorylation was ≥90% in ≥3 subjects in either dose group.The SRC will decide whether to initiate an extension study for that dose group and its subsequent dose groups at the same time as the dose escalation to the next dose group. Subjects in the dose escalation phase will be administered BID every 28 days in 1 cycle, with ≥8h between doses, fasting for at least 2 hours before and at least 1 hour after dosing with approximately 240mL of water (subject to adjustment based on data results from the dose escalation phase) . If initiation was determined, the dose group identified for initiation and its subsequent dose group extension studies were further enrolled in 14 to 17 cases \[a total of 20 cases in each dose group, with FLT3 mutation-positive (FLT3 internal tandem repeat (ITD) and/or FLT3 tyrosine kinase structural domain (TKD) mutation-positive subjects enrolled in at least 10 cases\] to further define the final RP2D.

A Study to Evaluate the STI-8591 in Subjects With Advanced Acute Myeloid Leukemia (AML)

A Multicenter, Open, Dose Escalation and Dose Expansion Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of STI-8591 in Subjects With Advanced Acute Myeloid Leukemia (AML)

Assessing the incidence of adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5)

Assessment of the pharmacokinetic profile of STI-8591 and its major metabolites (if any) in advanced AML:AUC(area under the concentration-time curve)

Assessment of the pharmacokinetic profile of STI-8591 and its major metabolites (if any) in advanced AML:Tmax (time to peak)

Assessment of the pharmacokinetic profile of STI-8591 and its major metabolites (if any) in advanced AML:Cmax(peak concentration)

Assessment of the percentage of biomarker changes relative to baseline for STI-8591 in advanced AML

Assessing the initial effectiveness of STI-8591 in advanced AML:CRc, defined as CR, CRh and CRi as judged according to ELN2022 criteria.

Assessing the initial effectiveness of STI-8591 in advanced AML:CR rate, defined as the CR rate judged according to ELN 2022 criteria.

Assessing the initial effectiveness of STI-8591 in advanced AML:ORR, defined as CR, CRh, CRi, MLFS and PR as judged by ELN2022 criteria.

Assessing the initial effectiveness of STI-8591 in advanced AML:DoR, defined as the time between the subject's first achievement of ORR and the first detection of recurrent disease, treatment failure, or death from any cause, whichever occurs first.

Assessing the initial effectiveness of STI-8591 in advanced AML:EFS, defined as the time from the start of the subject's enrollment to the occurrence of any event (treatment failure/relapse after CR, CRh or CRi/permanent termination of treatment for any reason/death from any cause), whichever occurs first.

Assessing the initial effectiveness of STI-8591 in advanced AML:PFS, defined as the time between the subject's first study treatment and the onset of treatment failure or death from any cause, whichever occurs first.

Assessing the initial effectiveness of STI-8591 in advanced AML:LFS, defined as the time between the first attainment of CRc and the first detection of recurrent disease or death from any cause, whichever occurs first.

Assessing the initial effectiveness of STI-8591 in advanced AML:OS, defined as the time between the subject's first study treatment and death from any cause.

Zhejiang ACEA Pharmaceutical Co. Ltd.

Part 1 of the study is a sequential dose-escalation evaluation of AKN-028. Part 1 started as an accelerated intra-patient dose escalation design in one patient at a time (the N=1 portion), and has switched to standard 3 + 3 design with inter-cohort dose escalation when AUC of 12 μM\*hrs has been reached. Starting dose of AKN-028 was 60 mg twice a day.

During Part 2 of the study AKN-028 will be administered at the dose level selected in Part 1. Patients will be treated for a maximum of 3 cycles (first cycle of 14 days followed by 2 cycles of 21 days), with at least a 7-day treatment-free period between cycles. Patients with significant benefit after 3rd cycle may continue treatment at discretion of the investigator for as long as the patient continues to show significant benefit.

AKN-028

Martin Höglund, MD, PhD

This Phase 1/2 study consists of two parts. The purpose of Part 1 of the study is to examine the safety and tolerability of AKN-028 and to determine the recommended dose of AKN-028 for further evaluation in Part 2 of the study in patients with Acute Myelogenous Leukemia (AML). The purpose of Part 2 of the study is to determine safety and efficacy in patients with AML.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the STI-8591 in Subjects With Advanced Acute Myeloid Leukemia (AML)	NCT05947344	AML, Adult	STI-8591	18 Years -	Zhejiang ACEA Pharmaceutical Co. Ltd.
Safety Study of AKN-028 in Patients With Acute Myelogenous Leukemia	NCT01573247	Acute Myeloid L...	AKN-028	18 Years -	Akinion Pharmaceuticals AB
Safety Study of AKN-028 in Patients With Acute Myelogenous Leukemia	NCT01573247	Acute Myeloid L...	AKN-028	18 Years -	Akinion Pharmaceuticals AB
A Study to Evaluate the STI-8591 in Subjects With Advanced Acute Myeloid Leukemia (AML)	NCT05947344	AML, Adult	STI-8591	18 Years -	Zhejiang ACEA Pharmaceutical Co. Ltd.

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