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    Clinical Trial Results:
    A multi-center, open-label, single-arm Phase I dose-escalation and Phase II dose-expansion study to evaluate the safety, tolerability, PK characteristics and anti-tumor activity of FCN-159 in adult and pediatric participants with neurofibromatosis type 1

    Summary
    EudraCT number
    		 2021-001572-42
    Trial protocol
    		 ES   IT   PL  
    Global end of trial date
    23 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Feb 2026
    First version publication date
    20 Feb 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    FCN-159-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04954001
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Shanghai Fosun Pharmaceutical Development Co., Ltd.
    Sponsor organisation address
    No. 1289, Yishan Road, Xuhui District, Shanghai, China, 200233
    Public contact
    Project Management, Shanghai Fosun Pharmaceutical Development Co., Ltd., +86 21- 33987558, chenleilei@fosunpharma.com
    Scientific contact
    Project Management, Shanghai Fosun Pharmaceutical Development Co., Ltd., +86 21- 33987558, chenleilei@fosunpharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Jun 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Sep 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Phase I: -To evaluate the safety and tolerability of FCN-159 administered PO daily. -To determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Phase II: -To assess the efficacy of FCN-159 per REiNS criteria.
    Protection of trial subjects
    The clinical study protocol, ICF, eCRF, and other relevant materials for this study were approved by the IEC before the start of the study. IEC strictly followed the requirements of relevant laws and regulations to review these materials and issue approval files after approval. The entire trial process of this study complied with relevant laws and regulations, Good Clinical Practice, and the principles of the Declaration of Helsinki (2013). The ICF must be signed and dated by patients or their legal representatives, and the investigator who performs the informed consent process or the representative before any drug administration.
    Background therapy
    		 The commonly used concomitant medications were supportive care for the target disease, corrective medications for adverse events, and treatment of medical history, including dermatological antibiotics and chemotherapy drugs, anti-inflammatory and anti-rheumatic drugs, and systemic anti-bacterial drugs, analgesics and systemic antihistamines, etc.
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    16 Mar 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 35 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 82
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    Spain: 1
    Worldwide total number of subjects
    86
    EEA total number of subjects
    1
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    86
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Phase I: a total of 19 Chinese patients (3 in the 4 mg dose group, 4 in the 6 mg dose group, 8 in the 8 mg dose group, and 4 in the 12 mg dose group) and 1 U.S. patient (8 mg dose group); Phase II: 63 Chinese patients and 3 non-Chinese patients (2 U.S. patients and 1 Spanish patient).

    Pre-assignment
    Screening details
    		 Adult patients diagnosed with symptomatic Neurofibromatosis type 1 with Plexiform neurofibroma (NF1 with PN) rwith PNs that was inoperable or had postoperative residual/recurrence.

    Period 1
    Period 1 title
    Treatment period - Phase I and Phase II (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    This is an open-label study

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase I - 4 mg FCN-159
    Arm description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 4 mg FCN-159.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FCN-159
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    4 mg FCN-159 tablets were orally administered once daily, for continuous use, with 28 days as a cycle.

    Arm title
    		 Phase I - 6 mg FCN-159
    Arm description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 6 mg FCN-159.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FCN-159
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    6 mg FCN-159 tablets were orally administered once daily, for continuous use, with 28 days as a cycle.

    Arm title
    		 Phase I - 8 mg FCN-159
    Arm description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 8 mg FCN-159.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FCN-159
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    8 mg FCN-159 tablets were orally administered once daily, for continuous use, with 28 days as a cycle.

    Arm title
    		 Phase I - 12 mg FCN-159
    Arm description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 12 mg FCN-159.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FCN-159
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    12 mg FCN-159 tablets were orally administered once daily, for continuous use, with 28 days as a cycle.

    Arm title
    		 Phase II - 8 mg FCN-159
    Arm description
    		 Participants enrolled in Phase II dose-expansion clinical trial assigned to receive Recommended Phase II dose (RP2D) of 8 mg FCN-159.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FCN-159
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    8 mg FCN-159 tablets were orally administered once daily, for continuous use, with 28 days as a cycle.

    Number of subjects in period 1
    		Phase I - 4 mg FCN-159 Phase I - 6 mg FCN-159 Phase I - 8 mg FCN-159 Phase I - 12 mg FCN-159 Phase II - 8 mg FCN-159
    Started
    3
    4
    9
    4
    66
    Completed
    3
    4
    9
    3
    54
    Not completed
    0
    0
    0
    1
    12
         Consent withdrawn by subject
    -
    -
    -
    -
    8
         Adverse event, non-fatal
    -
    -
    -
    1
    1
         Other
    -
    -
    -
    -
    2
         Death
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase I - 4 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 4 mg FCN-159.

    Reporting group title
    Phase I - 6 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 6 mg FCN-159.

    Reporting group title
    Phase I - 8 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 8 mg FCN-159.

    Reporting group title
    Phase I - 12 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 12 mg FCN-159.

    Reporting group title
    Phase II - 8 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase II dose-expansion clinical trial assigned to receive Recommended Phase II dose (RP2D) of 8 mg FCN-159.

    Reporting group values
    		 Phase I - 4 mg FCN-159 Phase I - 6 mg FCN-159 Phase I - 8 mg FCN-159 Phase I - 12 mg FCN-159 Phase II - 8 mg FCN-159 Total
    Number of subjects
    		 3 4 9 4 66 86
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 3 4 9 4 66 86
    Gender categorical
    Units: Subjects
        Female
    		 0 0 6 3 28 37
        Male
    		 3 4 3 1 38 49

    End points

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    End points reporting groups
    Reporting group title
    Phase I - 4 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 4 mg FCN-159.

    Reporting group title
    Phase I - 6 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 6 mg FCN-159.

    Reporting group title
    Phase I - 8 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 8 mg FCN-159.

    Reporting group title
    Phase I - 12 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 12 mg FCN-159.

    Reporting group title
    Phase II - 8 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase II dose-expansion clinical trial assigned to receive Recommended Phase II dose (RP2D) of 8 mg FCN-159.

    Subject analysis set title
    Phase II - 8 mg FCN-159 - ITT set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intent-to-treat (ITT) set: It included patients who signed the informed consent form (ICF) and had received at least one dose of FCN-159 Tablets

    Primary: Phase I - The occurrence of dose-limiting toxicity (DLT)

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    End point title
    		 Phase I - The occurrence of dose-limiting toxicity (DLT) [1] [2]
    End point description
    DLT analysis set: All patients who met the DLT evaluation criteria enrolled in the dose escalation part, regardless of whether DLT occurred during the DLT observation period. DLT = Dose-Limited Toxicity * The results present information only for Chinese participants.
    End point type
    Primary
    End point timeframe
    28 days after the dose of FCN-159
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was done for this end point
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point is applicable only for arms in Phase I.
    End point values
    		 Phase I - 4 mg FCN-159 Phase I - 6 mg FCN-159 Phase I - 8 mg FCN-159 Phase I - 12 mg FCN-159
    Number of subjects analysed
    3
    3
    6
    3
    Units: number
        Subjects with any TEAE
    0
    0
    1
    3
        DLT of Grade 3: folliculitis
    0
    0
    1
    3
    No statistical analyses for this end point

    Primary: Phase I - Maximum tolerated dose and recommended Phase II dose (RP2D) in clinical practice

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    End point title
    		 Phase I - Maximum tolerated dose and recommended Phase II dose (RP2D) in clinical practice [3] [4]
    End point description
    MTD is defined as the maximum dose level with a DLT incidence rate of < 33% (0/3 or 1/6 cases). After integrating the Phase I PK, PD, efficacy, and safety data, it was decided to set the adult RP2D at 8 mg after full discussion at the Safety Management Committee (SMC) meeting. * The results present information only for Chinese participants.
    End point type
    Primary
    End point timeframe
    Approximately 6-9 months for MTD and RP2D (phase I duration)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was done for this end point
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point is applicable only for arms in Phase I.
    End point values
    		 Phase I - 4 mg FCN-159 Phase I - 6 mg FCN-159 Phase I - 8 mg FCN-159 Phase I - 12 mg FCN-159
    Number of subjects analysed
    3
    3
    6
    3
    Units: percent
    number (not applicable)
        Subjects with any TEAE
    0
    0
    16.7
    100
    No statistical analyses for this end point

    Primary: Phase II - ORR assessed by the investigator: Best overall response

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    End point title
    		 Phase II - ORR assessed by the investigator: Best overall response [5]
    End point description
    Objective response rate (ORR) is defined as Proportion of patients achieving confirmed disease response (Complete response (CR) or Partial response (PR)). CR is defined as the disappearance of the target lesion. PR is defined as a ≥20% reduction in the volume of the target PN from baseline. Both CR and PR were confirmed by reassessment over at least 3 months. * The results present information only for Chinese participants.
    End point type
    Primary
    End point timeframe
    Through study completion, an average of 2 years
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was done for this end point
    End point values
    		 Phase II - 8 mg FCN-159 - ITT set
    Number of subjects analysed
    63
    Units: percent
    number (not applicable)
        Complete response (CR)
    0
        Partial response (PR)
    42.9
        Stable disease (SD)
    52.4
        Stable disease (SD) ≥ 6 months
    41.3
        Progressive disease (PD)
    0
        Not evaluable (NE)
    4.8
    No statistical analyses for this end point

    Primary: Phase II - ORR assessed by the investigator

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    End point title
    		 Phase II - ORR assessed by the investigator [6]
    End point description
    Objective response rate (ORR), defined as the proportion of patients with disease response (Responsive Disease, RD) confirmed using volumetric MRI analysis. Clinical benefit rate (CBR), defined as assessments including CR, PR, and SD lasting over 6 months. Disease control rate (DCR), defined as the percentage of cases with best response (PR or CR) and stable disease (SD) after treatment to the number of evaluable cases. Data includes subject of Intent-to-treat (ITT) set: It included patients who signed the informed consent form (ICF) and had received at least one dose of FCN-159 Tablets. * The results present information only for Chinese participants.
    End point type
    Primary
    End point timeframe
    Through study completion, an average of 2 years
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was done for this end point
    End point values
    		 Phase II - 8 mg FCN-159 - ITT set
    Number of subjects analysed
    63
    Units: percent
    number (confidence interval 95%)
        Objective Response Rate (ORR)
    42.9 (30.5 to 56.0)
        Clinical benefit rate (CBR)
    84.1 (72.7 to 92.1)
        Disease control rate (DCR)
    95.2 (86.7 to 99.0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Since the first administered dose till the end of safety follow up period (30 days of the last dose)
    Adverse event reporting additional description
    *The results present information only for Chinese participants.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Phase I - 4 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 4 mg FCN-159.

    Reporting group title
    Phase I - 6 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 6 mg FCN-159.

    Reporting group title
    Phase I - 8 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 8 mg FCN-159.

    Reporting group title
    Phase I - 12 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase I dose-finding clinical trial assigned to receive 12 mg FCN-159.

    Reporting group title
    Phase II - 8 mg FCN-159
    Reporting group description
    		 Participants enrolled in Phase II dose-expansion clinical trial assigned to receive Recommended Phase II dose (RP2D) of 8 mg FCN-159.

    Serious adverse events
    		 Phase I - 4 mg FCN-159 Phase I - 6 mg FCN-159 Phase I - 8 mg FCN-159 Phase I - 12 mg FCN-159 Phase II - 8 mg FCN-159
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    13 / 63 (20.63%)
         number of deaths (all causes)
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Vertebrobasilar artery dissection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Hemolytic anemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Rhegmatogenous retinal detachment
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    IgA nephropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Soft tissue infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 63 (3.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase I - 4 mg FCN-159 Phase I - 6 mg FCN-159 Phase I - 8 mg FCN-159 Phase I - 12 mg FCN-159 Phase II - 8 mg FCN-159
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 4 (100.00%)
    8 / 8 (100.00%)
    4 / 4 (100.00%)
    63 / 63 (100.00%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    5 / 8 (62.50%)
    0 / 4 (0.00%)
    25 / 63 (39.68%)
         occurrences all number
    0
    3
    5
    0
    25
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 8 (12.50%)
    3 / 4 (75.00%)
    25 / 63 (39.68%)
         occurrences all number
    0
    2
    1
    3
    25
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    28 / 63 (44.44%)
         occurrences all number
    0
    2
    0
    1
    28
    Urinary occult blood positive
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    3 / 8 (37.50%)
    1 / 4 (25.00%)
    20 / 63 (31.75%)
         occurrences all number
    0
    1
    3
    1
    20
    Weight increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    3 / 8 (37.50%)
    3 / 4 (75.00%)
    17 / 63 (26.98%)
         occurrences all number
    0
    1
    3
    3
    17
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    4 / 8 (50.00%)
    2 / 4 (50.00%)
    18 / 63 (28.57%)
         occurrences all number
    0
    1
    4
    2
    18
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    17 / 63 (26.98%)
         occurrences all number
    0
    2
    1
    1
    17
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    4 / 4 (100.00%)
    18 / 63 (28.57%)
         occurrences all number
    0
    0
    0
    4
    18
    Protein urine present
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    3 / 8 (37.50%)
    1 / 4 (25.00%)
    13 / 63 (20.63%)
         occurrences all number
    0
    3
    3
    1
    13
    Electrocardiogram T wave abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    14 / 63 (22.22%)
         occurrences all number
    0
    1
    0
    0
    14
    Blood uric acid increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    10 / 63 (15.87%)
         occurrences all number
    0
    3
    2
    0
    10
    pH urine decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    4 / 8 (50.00%)
    0 / 4 (0.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    3
    4
    0
    5
    Specific gravity urine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    4 / 8 (50.00%)
    0 / 4 (0.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    3
    4
    0
    5
    Bile acids increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    9 / 63 (14.29%)
         occurrences all number
    0
    2
    0
    1
    9
    Blood urea increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    8 / 63 (12.70%)
         occurrences all number
    0
    3
    2
    0
    8
    Urobilinogen urine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    3
    2
    0
    5
    QRS axis abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    3 / 4 (75.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    1
    1
    3
    5
    Urine ketone body present
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    3 / 8 (37.50%)
    2 / 4 (50.00%)
    3 / 63 (4.76%)
         occurrences all number
    0
    1
    3
    2
    3
    pH urine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    2
    1
    0
    5
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    2 / 63 (3.17%)
         occurrences all number
    0
    3
    2
    0
    2
    Immunoglobulins increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    2 / 63 (3.17%)
         occurrences all number
    0
    1
    2
    0
    2
    Prealbumin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    3 / 63 (4.76%)
         occurrences all number
    0
    0
    2
    0
    3
    White blood cells urine positive
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    1
    2
    0
    1
    Cardiac disorders
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    3 / 8 (37.50%)
    0 / 4 (0.00%)
    12 / 63 (19.05%)
         occurrences all number
    0
    3
    3
    0
    12
    Mitral valve incompetence
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    11 / 63 (17.46%)
         occurrences all number
    0
    3
    2
    0
    11
    Sinus arrhythmia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    8 / 63 (12.70%)
         occurrences all number
    0
    1
    2
    0
    8
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    13 / 63 (20.63%)
         occurrences all number
    0
    0
    2
    0
    13
    Gastrointestinal disorders
    Mouth ulceration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    3 / 4 (75.00%)
    37 / 63 (58.73%)
         occurrences all number
    0
    0
    1
    3
    37
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    3 / 8 (37.50%)
    2 / 4 (50.00%)
    28 / 63 (44.44%)
         occurrences all number
    0
    2
    3
    2
    28
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    4 / 8 (50.00%)
    2 / 4 (50.00%)
    11 / 63 (17.46%)
         occurrences all number
    0
    0
    4
    2
    11
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    5 / 8 (62.50%)
    0 / 4 (0.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    2
    5
    0
    5
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    15 / 63 (23.81%)
         occurrences all number
    0
    0
    1
    1
    15
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    13 / 63 (20.63%)
         occurrences all number
    0
    0
    0
    1
    13
    Pulmonary mass
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    6 / 63 (9.52%)
         occurrences all number
    0
    3
    0
    1
    6
    Skin and subcutaneous tissue disorders
    Folliculitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    4 / 8 (50.00%)
    4 / 4 (100.00%)
    49 / 63 (77.78%)
         occurrences all number
    0
    1
    4
    4
    49
    Paronychia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    3 / 8 (37.50%)
    3 / 4 (75.00%)
    35 / 63 (55.56%)
         occurrences all number
    0
    2
    3
    3
    35
    Dermatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 4 (75.00%)
    25 / 63 (39.68%)
         occurrences all number
    0
    0
    0
    3
    25
    Alopecia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    4 / 8 (50.00%)
    3 / 4 (75.00%)
    20 / 63 (31.75%)
         occurrences all number
    0
    1
    4
    3
    20
    Urticaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    18 / 63 (28.57%)
         occurrences all number
    0
    0
    0
    1
    18
    Dry skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    14 / 63 (22.22%)
         occurrences all number
    0
    0
    1
    2
    14
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    2 / 4 (50.00%)
    10 / 63 (15.87%)
         occurrences all number
    0
    0
    2
    2
    10
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    4 / 63 (6.35%)
         occurrences all number
    0
    2
    2
    0
    4
    Drug eruption
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    3 / 63 (4.76%)
         occurrences all number
    0
    2
    2
    0
    3
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 8 (12.50%)
    3 / 4 (75.00%)
    37 / 63 (58.73%)
         occurrences all number
    0
    2
    1
    3
    37
    COVID-19
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    17 / 63 (26.98%)
         occurrences all number
    0
    3
    2
    0
    17
    Pharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 4 (50.00%)
    13 / 63 (20.63%)
         occurrences all number
    0
    0
    0
    2
    13
    Metabolism and nutrition disorders
    Hypercholesterolemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    13 / 63 (20.63%)
         occurrences all number
    0
    0
    0
    1
    13
    Dyslipidaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    5 / 63 (7.94%)
         occurrences all number
    0
    2
    2
    0
    5
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    2
    1
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Dec 2020
    Protocol, Version 2.1 • Data summary from the first-in-human study of FCN-159 in patients with melanoma (including clinical PK and safety data for 0.2 mg-6 mg) was added as the basis for FCN-159 dose bridging in patients with NF1 • The starting dose was increased from 1 mg to 4 mg based on updated FCN-159 data in patients with melanoma • The last 13 lung cancer-specific questions were deleted from the EORTC QLQ-C30 (V3.0) quality-of-life scale in Attachment 12.
    19 Feb 2021
    Protocol, Version 3.0 • Patient numbers were increased (42 adults in Phase I, 55 adults in Phase II) • Study sites were expanded (~10 sites for Phase I, ~30 sites for Phase II) • CYP2C9 enzyme polymorphism testing was added. • Treatment duration was modified to "the administration of FCN-159 Tablets was continued until progressive disease or other criteria for termination of treatment were met" • Tumor assessment frequency was adjusted from "every 3 cycles in the first year, every 6 cycles thereafter" to "every 4 cycles in the first 2 years, every 6 cycles thereafter" • Functional scales were added
    19 Mar 2021
    Protocol, Version 3.1 • Safety Management Committee (SMC) was added • Management and prevention of adverse events (e.g., skin toxicity, hepatotoxicity, gastrointestinal events, LVEF, ocular toxicity) were refined
    22 May 2021
    Protocol, Version 3.2 • PD testing was added in Phase I to better analyze dose-response relationships and determine the optimal recommended phase II dose • The patient age range was revised to ">18 and ≤70 years • Both Phase I and II enrollment populations were revised to "patients with symptomatic plexiform fibroma" • Strong CYP2C8 and CYP2C9 inhibitors or inducers (including moderate inducers) as prohibited drugs were added • PK sampling times were adjusted based on tumor assessment cycles • It was specified that efficacy assessment would follow REiNS criteria
    13 Oct 2021
    Protocol, Version 4.0 • 3D laser scanning for NF1 with PNs evaluation was deleted • The adult RP2D of 8 mg was confirmed by the SMC meeting based on Phase I data, and this information was added • Specific ophthalmologic examination items were added to avoid inconsistent items in eye examination of each site • A single ECG was changed to three ECGs, and ECG frequency was reduced in Phase II
    11 Jun 2022
    Protocol, Version 5.0 • The administration under fasting was adjusted to not requiring fasting state based on the food effect test. • Family history of sudden cardiac death, acute neurological events, and concurrent use of anticoagulants were added as exclusion criteria. • Pharmacokinetic blood collection time points were updated. • ERK phosphorylation inhibition assessment was updated. • Amylase testing was replaced with lipase testing during the screening/baseline period. • Ophthalmologic function and airway function evaluations for orbital PN were deleted. • Delete impulse concussion pulmonary function methodImpulse oscillometry was deleted. • Assessments for plexiform neurofibromas affecting speech/swallowing were deleted
    29 Dec 2023
    Protocol, Version 6.2 • The investigator-assessed ORR was adjusted to the primary endpoint, while the IRC-assessed ORR was adjusted to a secondary endpoint

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/37400844
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