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

A Phase II Clinical Study to Evaluate the Safety & Tolerability, Antitumor Activity, and Pharmacokinetics of FCN-338 in Combination With Azacitidine or Chemotherapy in Patients With Myeloid Neoplasms

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

Study Overview

• Status: Active, not recruiting
• Conditions: Safety; Antitumor Activity; PK Profile
• Intervention / Treatment: Combination product: FCN-338 + Azacitidine; Combination product: FCN-338 + erythromycin+ Ara-C

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 Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Wuhan, China
    • Union hospital tongjimedical college huzhong university of science and technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusive Criteria

1. Age ≥18 years.
2. Cohort A: Patients diagnosed with R/RAML (≥5% blasts in the bone marrow) according to the WHO 2016 criteria [excluding acute promyelocytic leukemia (APL) and BCR-ABL positive AML], meeting any of the following definitions:

1) Relapsed AML: Reappearance of leukemic cells in peripheral blood or ≥5% blasts in bone marrow after complete remission (CR, CRi) (excluding other causes such as bone marrow regeneration after consolidation treatment) or infiltration of leukemic cells outside the marrow; 2) Refractory AML: Ineffective after two cycles of standard treatment; Relapsed within 12 months after CR followed by consolidation treatment; Relapsed after 12 months but ineffective with standard chemotherapy; Relapsed two or more times; With persistent extramedullary leukemia.

3. Cohort B: Patients diagnosed with 1L fit AML according to the WHO 2016 criteria [excluding acute promyelocytic leukemia (APL) and BCR-ABL positive AML].

4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 5. Expected survival time ≥ 3 months. 6. Adequate bone marrow and organ function. Exclusive Criteria

1. Patients with diagnosis of APL or BCR-ABL-positive AML patients or a history of prior myeloproliferative disease (MPN).
2. With known leukemic infiltration of the central nervous system.
3. Have received allogeneic hematopoietic stem cell transplantation or overt immune cell therapy, or autologous hematopoietic stem cell transplantation within 1 year.
4. Have active fungal, bacterial and/or viral infections including, but not limited to, active Human Immunodeficiency Virus (HIV), viral hepatitis B or C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: relapse/refractory (R/R) AML	Combination product: FCN-338 + Azacitidine; FCN-338 (400 or 600 mg, PO, QD, D1-28) combined with azacitidine (75mg/m², SC, QD, D1-7), 28 days/cycle
Experimental: 1L fit AML	Combination product: FCN-338 + erythromycin+ Ara-C; Induction phase: FCN-338(600 mg, QD, D1-14) , erythromycin (60 mg/m², IV, QD , D1-3) and Ara-C (100 mg/m², IV, QD, D1-7) for 1 to 2 cycles. Consolidation phase: FCN-338(600 mg, QD, D1-14) ,Ara-C (1 to 3 g/m²/12h, 6 doses) for 3 to 4 cycles Maintenance phase:FCN-338(600 mg, QD, D1-14) , azacitidine (50 mg/m², SC, QD, D1-5) for the first 12 cycles and FCN-338 (600 mg, QD, D1-14) alone for the rest 12 cycles

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfusion Independence	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.	From the first dose to the end of maintenance phase, assessed up to 30 months
Time to remission	Defined as the time from the first dose to the first observation of CR/CRi/MLFS	From the first dose to the first observation of CR/CRi/MLFS, assessed up to 2 months
Event-free survival	Defined as the time from the first dose to induction failure or relapse or death from any cause (whichever occours first).	From the first dose to induction failure or relapse or death from any cause (whichever occours first), assessed up to 54 months
Duration of remission	Defined as the time from the first observation of CR/CRi/MLFS to tumor progression or death from any cause(whichever occours first).	From the first observation of CR/CRi/MLFS to tumor progression or death from any cause(whichever occours first), assessed up to 54 months
Overall survival	Defined as the time from the first dose to death from any cause.	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
Incidence of treatment-emergent adverse events(TEAEs) and treatment-related adverse events (TRAEs) [Safety and Tolerability]	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.	From the first dose to 30 days after the last dose or the initiation of new antitumor therapy (whichever occours first).
Cmax of FCN-338	Pharmacokinetics of FCN-338 by assesment of the maximum plasma concentration	Up to 24 hours postdose
AUC0-t of FCN-338	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	Up to 24 hours postdose
AUC0-24 of FCN-338	Pharmacokinetics of FCN-338 by assesment of the Area Under The Plasma Concentration Time Curve From Time 0 To The 24 hours postdose	Up to 24 hours postdose
AUC0-∞ of FCN-338	Pharmacokinetics of FCN-338 by assesment of The Plasma Concentration Time Curve From Time 0 To Infinity	Up to 24 hours postdose
Tmax of FCN-338	Pharmacokinetics of FCN-338 by assesment of Time To Maximum Observed Plasma Concentration	Up to 24 hours postdose
t1/2 of FCN-338	Pharmacokinetics of FCN-338 by assesment of Terminal Half-life	Up to 24 hours postdose
CL/F of FCN-338	Pharmacokinetics of FCN-338 by assesment of Apparent Clearance Of Drug From Plasma After Oral Administration	Up to 24 hours postdose
Vd/F of FCN-338	Pharmacokinetics of FCN-338 by assesment of Apparent Volume Of Distribution	Up to 24 hours postdose
Css_max of FCN-338	Pharmacokinetics of FCN-338 by assesment of Maximum Observed Plasma Concentration At Steady State	Up to 24 hours postdose
Css_av of FCN-338	Pharmacokinetics of FCN-338 by assesment of the Average concentration At Steady State	Up to 24 hours postdose
AUCss of FCN-338	Pharmacokinetics of FCN-338 by assesment of the Area Under The Plasma Concentration Time Curve within dosing interval At Steady State	Up to 24 hours postdose
DF of FCN-338	Pharmacokinetics of FCN-338 by assesment of fluctuation	Up to 24 hours postdose
MRT	Pharmacokinetics of FCN-338 by assesment of Mean residence time	Up to 24 hours postdose
Kel of FCN-338	Pharmacokinetics of FCN-338 by assesment of the Terminal rate constant.	Up to 24 hours postdose
Css_min of FCN-338	Pharmacokinetics of FCN-338 by assesment of Trough Concentration At Steady State	Up to 24 hours postdose

Collaborators and Investigators

• Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Collaborators: Beijing Fosun Pharmaceutical Technology Development Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; safety; BCL-2 inhibitor; antitumor activity; PK profile
• Additional Relevant MeSH Terms: Neoplasms; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Protein Synthesis Inhibitors; Azacitidine; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate
• Other Study ID Numbers: FCN-338-II201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No