This is a rare disease, single-arm, open-label,multi-center, non-randomized Phase 2 clinical study to evaluate the efficacy, safety, and pharmacokinetic characteristics of FCN-159 monotherapy in pediatric patients with refractory/recurrent Langerhans cell histiocytosis (LCH).
Age 2-16 (inclusive)
Patients with histologically confirmed Langerhans cell histiocytosis (LCH) diagnosed by the central laboratory.
If sufficient tumor tissue samples and peripheral blood samples are available, central laboratory biomarker testing is required as follows: including but not limited to ERBB3, BRAF, ARAF, HRAS, KRAS, NRAS, MEK (MAP2K1 and MAP2K2), and other MEK upstream genes.If inability to get tissue, the gene testing results from a local laboratory also can be accepted.
Patients who have received at least prior first-line systemic treatment, defined as treatment including vinblastine (VBL) and glucocorticoids for at least 2 weeks. VBL can be substituted with vincristine (VCR) or vindesine (VDS). Alternatively, patients may be unable to tolerate chemotherapy due to severe chemotherapy toxicity. Inability to tolerate chemotherapy is defined as one of the following: Severe liver impairment (liver enzyme elevation ≥ 5 × upper limit of normal (ULN) and bilirubin elevation ≥ 1.5 × ULN), severe neurotoxicity related to vinca alkaloids, chemotherapy-related intracranial hypertension, or grade 4 bone marrow depression with severe infection (sepsis, severe pneumonia, etc.) after chemotherapy.
Chemotherapy, targeted therapy, immunotherapy, biologic therapy, or herbal anti-tumor therapy for LCH within 4 weeks or < 5 half-lives (whichever is shorter)before the start of the study drug .
Strong CYP3A4, CYP2C8, and CYP2C9 inhibitors or inducers within 14 days before the start of the study drug, except for topical skin application.
Gowth factors that promote platelet or white blood cell count or function within 7 days before the start of the study drug.
Radiotherapy or major surgical treatment (including craniotomy, thoracotomy, laparotomy, open bone or joint surgery, etc.) within 4 weeks before the start of the study drug.
Single group
FCN-159
Drug5mg/m² (Maximum dose does not exceed 8mg, the recommended oral dose for adults), orally, once daily, continuously for 28 days per cycle.
Objective Response Rate (ORR) Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC)
ORR Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC) is defined as the percentage of participants who achieved a best overall response of CMR or PMR assessed by IRC .
Objective Response Rate (ORR) Evaluated by Investigator Based on PET Response Criteria (PRC) and Langerhans Cell Histiocytosis Evaluation and Treatment Guidelines (Histiocyte Society, April 2009, hereinafter referred to as "Guidelines")
The ORR Evaluated by Investigator Based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR assessed by investigator. The ORR Evaluated by Investigator Based on "Guidelines" is defined as the percentage of participants who achieved confirmed NAD or AD-better assessed by investigator.
Disease Control Rate (DCR) Evaluated by Investigator Based on PET Response Criteria (PRC) and "Guidelines".
The DCR Evaluated by Investigator based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR or SMD assessed by investigator. The DCR Evaluated by Investigator Based on "Guidelines" is defined as the percentage of participants who achieved a confirmed NAD or AD-better or AD-stable assessed by investigator.
Clinical benefit rate (CBR) Evaluated by Investigator Based on PRC and "Guidelines".
The CBR Evaluated by Investigator based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR or SMD for a duration of ≥ 24 weeks assessed by investigator. The CBR Evaluated by Investigator Based on "Guidelines" is defined as the percentage of participants who achieved confirmed NAD or AD-better or AD stable for a duration of ≥ 24 weeks assessed by investigator.
Time to Response (TTR) Evaluated by Investigator Based on PET Response Criteria (PRC) and "Guidelines"
The TTR Evaluated by Investigator based on PRC is defined as the time from the first documented achievement of CMR or PMR (whichever comes first) assessed by investigator. The TTR Evaluated by Investigator based on the "Guidelines" criteria is defined as the time from the first documented achievement of NAD or AD-better (whichever comes first) assessed by investigator.
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