Clinical trial NCT06858618: FCN-338 in Combination With Azacitidine or Chemotherapy in Myeloid Neoplasms
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Safety
Antitumor Activity
PK Profile
Keywords: BCL-2 inhibitor
Acute Myeloid Leukemia
safety
antitumor activity
PK profile
Lead sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Beijing Fosun Pharmaceutical Technology Development Co., Ltd.
First posted: 2025-03-05
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of DLT
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Title: composite CR rate (CRc)
timeFrame: From the first dose to the end of maintenance phase, assessed up to 30 months
measure: Minimal residual disease (MRD) negative rate
timeFrame: From the first dose to the end of maintenance phase, assessed up to 30 months
Secondary outcomes:
measure: Transfusion Independence
timeFrame: From the first dose to the end of maintenance phase, assessed up to 30 months
measure: Time to remission
timeFrame: From the first dose to the first observation of CR/CRi/MLFS, assessed up to 2 months
measure: Event-free survival
timeFrame: From the first dose to induction failure or relapse or death from any cause (whichever occours first), assessed up to 54 months
measure: Duration of remission
timeFrame: From the first observation of CR/CRi/MLFS to tumor progression or death from any cause(whichever occours first), assessed up to 54 months
measure: Overall survival
timeFrame: 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
measure: Incidence of treatment-emergent adverse events(TEAEs) and treatment-related adverse events (TRAEs) [Safety and Tolerability]
timeFrame: From the first dose to 30 days after the last dose or the initiation of new antitumor therapy (whichever occours first).
measure: Cmax of FCN-338
timeFrame: Up to 24 hours postdose
measure: AUC0-t of FCN-338
timeFrame: Up to 24 hours postdose
measure: AUC0-24 of FCN-338
timeFrame: Up to 24 hours postdose
measure: AUC0-∞ of FCN-338
timeFrame: Up to 24 hours postdose
measure: Tmax of FCN-338
timeFrame: Up to 24 hours postdose
measure: t1/2 of FCN-338
timeFrame: Up to 24 hours postdose
measure: CL/F of FCN-338
timeFrame: Up to 24 hours postdose
measure: Vd/F of FCN-338
timeFrame: Up to 24 hours postdose
measure: Css_max of FCN-338
timeFrame: Up to 24 hours postdose
measure: Css_av of FCN-338
timeFrame: Up to 24 hours postdose
measure: AUCss of FCN-338
timeFrame: Up to 24 hours postdose
measure: DF of FCN-338
timeFrame: Up to 24 hours postdose
measure: MRT
timeFrame: Up to 24 hours postdose
measure: Kel of FCN-338
timeFrame: Up to 24 hours postdose
measure: Css_min of FCN-338
timeFrame: Up to 24 hours postdose
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union hospital tongjimedical college huzhong university of science and technology
Study officials:
References: