FCN-338 in Combination With Azacitidine or Chemotherapy in Myeloid Neoplasms

Phase 2

Active, not recruiting

• Conditions: Safety; Antitumor Activity; PK Profile

• Registration Number: NCT06858618
• Lead Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Brief Summary

This is a Phase 2, open-label, multicenter study to safety \& tolerability, antitumor activity, and pharmacokinetics of FCN-338 in Combination with szacitidine (AZA) or chemotherapy(erythromycin, cytarabine(Ara-C)) in Patients with myeloid neoplasms

Detailed Description

Primary Objectives:1.To assess the safety and tolerability of FCN-338 in combination with AZA or chemotherapy in patients with myeloid neoplasms. 2. To explore the antitumor activity of FCN-338 combination therapy in patients with myeloid neoplasms.

Secondary Objectives: 1. To assess the pharmacokinetic profile of the FCN-338 combination therapy in patients with myeloid neoplasms.2. To assess the transfusion independence rate in patients with myeloid neoplasms.

There were 2 cohorts based on different combination therapies and different indications.

Cohort A is FCN-338 combined with AZA (75mg/m², SC, QD, D1-7) for the treatment in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients.

Cohort B is FCN-338 combined with intensive chemotherapy for first line (1L) fit AML patients. During the induction phase, patients will be treated with erythromycin (60 mg/m², IV, QD , D1-3) and Ara-C (100 mg/m², IV, QD, D1-7). Patients achieving partial remission (PR) will repeat induction phase once, and patients who do not reach PR after first cycle of induction phase and those who do not achieve complete remission (CR)/Complete remission with incomplete hematological recovery (CRi)/morphologic leukemia-free state (MLFS) after two cycles of induction phase will receive other new antitumor treatments. Patients who achieve CR/CRi/MLFS will undergo consolidation phase with medium- to high-dose Ara-C (1 to 3 g/m²/12h, 6 doses) for 3 to 4 cycles, with the exact dose and number of cycles determined by investigator. Patients with intermediate- to high-risk according to the 2017 European Leukemia Net (ELN) stratification will undergo a total of 24 cycles of maintenance phase after completion of consolidation phase. Maintenance phase will consist of 24 cycles, FCN-338 in combination with AZA (50 mg/m², d1-5) for the first 12 cycles and FCN-338 alone for the rest 12 cycles. FCN-338 will be administered once daily (QD), D1-14 per cycle during induction phase, consolidation phase and maintenance phase.

Study Timeline

• Study Start: 2023-08-16
• Status Verified: 2025-01
• Study First Submitted: 2025-02-04
• Study First Submitted QC: 2025-02-27
• Last Update Submitted: 2025-02-27
• Study First Posted: 2025-03-05
• Last Update Posted: 2025-03-05
• Primary Completion: 2026-12-01
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Incidence of DLT	At the end of Cycle 1 (each cycle is 28 days)	Incidence of DLT in DLT observation period
Title: composite CR rate (CRc)	From the first dose to the end of maintenance phase, assessed up to 30 months	The proportion of CR, CRi and MLFS patients in the efficacy analysis set (EAS)
Minimal residual disease (MRD) negative rate	From the first dose to the end of maintenance phase, assessed up to 30 months	The proportion of AML patients with CR/CRi/MLFS who were negative for MRD.

Secondary Outcome Measures

Name	Time	Method
Overall survival	From the first dose to 30 days after the last dose or the initiation of new antitumor therapy (whichever occours first), assessed up to 30 months	Defined as the time from the first dose to death from any cause.
Incidence of treatment-emergent adverse events(TEAEs) and treatment-related adverse events (TRAEs) [Safety and Tolerability]	From the first dose to 30 days after the last dose or the initiation of new antitumor therapy (whichever occours first).	Safety will be evaluated by summarizing DLT, AE, changes in laboratory findings, and changes in vital signs. Adverse events will be summarized for the DLT observation period and the entire treatment period based on the DLT analysis set and the safety analysis set, respectively, and drug-related AEs, SAEs, AEs of toxicity grade ≥3, and AEs leading to discontinuation will be counted. The occurrence of DLT will be assessed specifically for the DLT analysis set.
AUC0-t of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of the Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration
AUC0-24 of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of the Area Under The Plasma Concentration Time Curve From Time 0 To The 24 hours postdose
AUC0-∞ of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of The Plasma Concentration Time Curve From Time 0 To Infinity
Tmax of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Time To Maximum Observed Plasma Concentration
t1/2 of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Terminal Half-life
CL/F of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Apparent Clearance Of Drug From Plasma After Oral Administration
Transfusion Independence	From the first dose to the end of maintenance phase, assessed up to 30 months	The proportion of independence on red blood cell (RBC) and platelet transfusions among those patients who were dependent on RBC and platelet transfusions at baseline.
Time to remission	From the first dose to the first observation of CR/CRi/MLFS, assessed up to 2 months	Defined as the time from the first dose to the first observation of CR/CRi/MLFS
Event-free survival	From the first dose to induction failure or relapse or death from any cause (whichever occours first), assessed up to 54 months	Defined as the time from the first dose to induction failure or relapse or death from any cause (whichever occours first).
Duration of remission	From the first observation of CR/CRi/MLFS to tumor progression or death from any cause(whichever occours first), assessed up to 54 months	Defined as the time from the first observation of CR/CRi/MLFS to tumor progression or death from any cause(whichever occours first).
Cmax of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of the maximum plasma concentration
Vd/F of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Apparent Volume Of Distribution
Css_max of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Maximum Observed Plasma Concentration At Steady State
Css_av of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of the Average concentration At Steady State
AUCss of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of the Area Under The Plasma Concentration Time Curve within dosing interval At Steady State
DF of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of fluctuation
MRT	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Mean residence time
Kel of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of the Terminal rate constant.
Css_min of FCN-338	Up to 24 hours postdose	Pharmacokinetics of FCN-338 by assesment of Trough Concentration At Steady State

Trial Locations

Locations (1)

Union hospital tongjimedical college huzhong university of science and technology; 🇨🇳 Wuhan, China