Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44409   clinical trials with a EudraCT protocol, of which   7418   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2 trial of Nirogacestat in Patients with Recurrent Ovarian Granulosa Cell Tumors

    Summary
    EudraCT number
    		 2022-001816-25
    Trial protocol
    		 PL  
    Global end of trial date
    14 Jul 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Jul 2026
    First version publication date
    18 Jul 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NIR-OGT-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05348356
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    SpringWorks Therapeutics, Inc.
    Sponsor organisation address
    100 Washington Blvd, Stamford, United States, 06902
    Public contact
    Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.com
    Scientific contact
    Communication Center, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.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
    28 Aug 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Jul 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the anti-tumor activity of nirogacestat in adult participants with relapsed/refractory ovarian granulosa cell tumors (OvGCT)
    Protection of trial subjects
    This study was conducted in accordance with the protocol and the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, and applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Sep 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 50
    Country: Number of subjects enrolled
    Poland: 3
    Worldwide total number of subjects
    53
    EEA total number of subjects
    3
    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)
    42
    From 65 to 84 years
    10
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 79 participants were screened, with 53 participants who enrolled and received study treatment (nirogacestat).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Nirogacestat Open-Label
    Arm description
    		 Nirogacestat 150 mg, by mouth, twice daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nirogacestat
    Investigational medicinal product code
    Other name
    PF-03084014, Ogsiveo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Nirogacestat 150 mg, by mouth, twice daily.

    Number of subjects in period 1
    		Nirogacestat Open-Label
    Started
    53
    Completed
    1
    Not completed
    52
         Adverse event, serious fatal
    1
         Consent withdrawn by subject
    4
         Physician decision
    8
         Disease progression
    38
         Clinical Progression
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Nirogacestat Open-Label
    Reporting group description
    		 Nirogacestat 150 mg, by mouth, twice daily.

    Reporting group values
    		 Nirogacestat Open-Label Total
    Number of subjects
    		 53 53
    Age Categorical
    Units: participants
        <45 years
    		 13 13
        >=45 years
    		 40 40
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.1 ( 12.85 ) -
    Sex: Female, Male
    Sex/Gender at birth (Customized)
    Units: participants
        Female
    		 53 53
        Male
    		 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 6 6
        Not Hispanic or Latino
    		 43 43
        Unknown or Not Reported
    		 4 4
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0
        Asian
    		 3 3
        Native Hawaiian or Other Pacific Islander
    		 0 0
        Black or African American
    		 4 4
        White
    		 37 37
        More than one race
    		 2 2
        Unknown or Not Reported
    		 7 7
    Region of Enrollment
    Units: Subjects
        United States
    		 50 50
        Poland
    		 3 3
    Baseline Height
    Units: meter
        arithmetic mean (standard deviation)
    		 1.632 ( 0.0611 ) -
    Baseline Weight
    Units: kilogram
        arithmetic mean (standard deviation)
    		 82.48 ( 19.672 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Nirogacestat Open-Label
    Reporting group description
    		 Nirogacestat 150 mg, by mouth, twice daily.

    Primary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    The percentage of participants with complete response (CR) + partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Full Analysis Set which consisted of all participants who received at least 1 dose of nirogacestat.
    End point type
    Primary
    End point timeframe
    2.5 years
    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: Statistical analyses were not planned for this endpoint.
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    53
    Units: percentage of participants
    0
    No statistical analyses for this end point

    Secondary: Overall Survival at Year 2

    		 Close Top of page
    End point title
    		 Overall Survival at Year 2
    End point description
    The number of participants who have not died of any cause by Year 2. Full Analysis Set which consisted of all participants who received at least 1 dose of nirogacestat.
    End point type
    Secondary
    End point timeframe
    2 years after first dose of study treatment
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    53
    Units: participants
    47
    No statistical analyses for this end point

    Secondary: Duration of Response

    		 Close Top of page
    End point title
    		 Duration of Response
    End point description
    The time from response (Complete Response [CR] + Partial Response [PR] using RECIST v.1.) to disease progression and/or death, in participants with CR or PR.
    End point type
    Secondary
    End point timeframe
    First day of every other cycle (each cycle is 28 days) for the first year, and then every 3 cycles thereafter until study completion (estimated to be an average of 2.5 years).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    0 [2]
    Units: months
    Notes
    [2] - Participants who had CR or PR.
    No statistical analyses for this end point

    Secondary: Progression Free Survival at 6 months (PFS-6)

    		 Close Top of page
    End point title
    		 Progression Free Survival at 6 months (PFS-6)
    End point description
    The number of participants without progression according to RECIST v1.1 or death at 6 months. Full Analysis Set which consisted of all participants who received at least 1 dose of nirogacestat.
    End point type
    Secondary
    End point timeframe
    First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days.
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    53
    Units: participants
    22
    No statistical analyses for this end point

    Secondary: Change from baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.

    		 Close Top of page
    End point title
    		 Change from baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.
    End point description
    Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit. Participants evaluable for outcome of change from baseline at Cycle 2 Day 1 in the FOSI score.
    End point type
    Secondary
    End point timeframe
    Baseline and at Cycle 2 Day 1 (cycle length is 28 days).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    49
    Units: score on a scale
        arithmetic mean (standard deviation)
    -1.1 ( 3.86 )
    No statistical analyses for this end point

    Secondary: Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    		 Close Top of page
    End point title
    		 Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
    End point description
    Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit. Participants evaluable for outcome of change from baseline at Cycle 3 Day 1 in the FOSI score.
    End point type
    Secondary
    End point timeframe
    Baseline and at Cycle 3 Day 1 (cycle length is 28 days).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    36
    Units: score on a scale
        arithmetic mean (standard deviation)
    -1.2 ( 4.00 )
    No statistical analyses for this end point

    Secondary: Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    		 Close Top of page
    End point title
    		 Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
    End point description
    Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit. Participants evaluable for the outcome of change from baseline at Cycle 4 Day 1 in the FOSI score.
    End point type
    Secondary
    End point timeframe
    Baseline and at Cycle 4 Day 1 (cycle length is 28 days).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    33
    Units: score on a scale
        arithmetic mean (standard deviation)
    -1.5 ( 3.08 )
    No statistical analyses for this end point

    Secondary: Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    		 Close Top of page
    End point title
    		 Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
    End point description
    Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit. Participants evaluable for the outcome of change from baseline at Cycle 5 Day 1 in the FOSI score.
    End point type
    Secondary
    End point timeframe
    Baseline and at Cycle 5 Day 1 (cycle length is 28 days).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    25
    Units: score on a scale
        arithmetic mean (standard deviation)
    -1.3 ( 3.36 )
    No statistical analyses for this end point

    Secondary: Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    		 Close Top of page
    End point title
    		 Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
    End point description
    Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit. Participants evaluable for the outcome of change from baseline in the FOSI score at end of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and at end of treatment (estimated to be an average of 5.5 months [minimum of 0 month and maximum of 33 months]).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    48
    Units: score on a scale
        arithmetic mean (standard deviation)
    -2.2 ( 4.48 )
    No statistical analyses for this end point

    Secondary: Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    		 Close Top of page
    End point title
    		 Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
    End point description
    Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit. Participants evaluable for the outcome of change from baseline in the FOSI score at safety follow-up.
    End point type
    Secondary
    End point timeframe
    Baseline and at safety follow-up (up to a maximum of 34 months).
    End point values
    		 Nirogacestat Open-Label
    Number of subjects analysed
    40
    Units: score on a scale
        arithmetic mean (standard deviation)
    -0.8 ( 3.75 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All SAEs and AEs were collected from the time of signing ICF until 30 days after the last dose of study treatment (an average of 5.5 months [minimum of 0 month and maximum of 33 months] and up to 34 months).
    Adverse event reporting additional description
    All SAEs and AEs were collected from the time of signing ICF until 30 days after the last dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Nirogacestat Open-Label
    Reporting group description
    		 Nirogacestat 150 mg, by mouth, twice daily.

    Serious adverse events
    		 Nirogacestat Open-Label
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 53 (22.64%)
         number of deaths (all causes)
    7
         number of deaths resulting from adverse events
    Investigations
    Electrocardiogram QT prolonged
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Cardio-respiratory arrest
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    Angina pectoris
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute myocardial infarction
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Encephalopathy
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Influenza like illness
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Colitis
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestinal obstruction
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary oedema
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Hidradenitis
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Gastroenteritis astroviral
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypomagnesaemia
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypophagia
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    Hypophosphataemia
    alternative dictionary used: MedDRA 27.1
         subjects affected / exposed
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Nirogacestat Open-Label
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    52 / 53 (98.11%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Vascular disorders
    Hypertension
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    5
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Fatigue
         subjects affected / exposed
    21 / 53 (39.62%)
         occurrences all number
    30
    Pyrexia
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    5
    Oedema peripheral
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    5
    Cough
         subjects affected / exposed
    17 / 53 (32.08%)
         occurrences all number
    25
    Epistaxis
         subjects affected / exposed
    8 / 53 (15.09%)
         occurrences all number
    8
    Nasal congestion
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    6
    Oropharyngeal pain
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    6
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    8
    Anxiety
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    6
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    6
    Neutrophil count decreased
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    4
    Weight decreased
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    4
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    7 / 53 (13.21%)
         occurrences all number
    7
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Headache
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    9
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    11
    Eye disorders
    Photopsia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Dry mouth
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Dyspepsia
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    7
    Flatulence
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Constipation
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    5
    Nausea
         subjects affected / exposed
    30 / 53 (56.60%)
         occurrences all number
    42
    Vomiting
         subjects affected / exposed
    20 / 53 (37.74%)
         occurrences all number
    28
    Abdominal pain
         subjects affected / exposed
    11 / 53 (20.75%)
         occurrences all number
    12
    Abdominal distension
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    6
    Stomatitis
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    6
    Diarrhoea
         subjects affected / exposed
    38 / 53 (71.70%)
         occurrences all number
    68
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Rash
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    4
    Dermatitis acneiform
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Rash maculo-papular
         subjects affected / exposed
    17 / 53 (32.08%)
         occurrences all number
    23
    Pruritus
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    6
    Alopecia
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    7
    Renal and urinary disorders
    Glycosuria
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    5
    Proteinuria
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    11
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    9
    Myalgia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Arthralgia
         subjects affected / exposed
    7 / 53 (13.21%)
         occurrences all number
    11
    Back pain
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    8
    Pain in extremity
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    COVID-19
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Sinusitis
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Skin infection
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    3
    Fungal infection
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    4
    Urinary tract infection
         subjects affected / exposed
    4 / 53 (7.55%)
         occurrences all number
    5
    Metabolism and nutrition disorders
    Hypermagnesaemia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    7
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    5
    Hypomagnesaemia
         subjects affected / exposed
    3 / 53 (5.66%)
         occurrences all number
    7
    Hypophosphataemia
         subjects affected / exposed
    15 / 53 (28.30%)
         occurrences all number
    32
    Hypokalaemia
         subjects affected / exposed
    10 / 53 (18.87%)
         occurrences all number
    25
    Hyperglycaemia
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    7
    Decreased appetite
         subjects affected / exposed
    6 / 53 (11.32%)
         occurrences all number
    11
    Hypocalcaemia
         subjects affected / exposed
    5 / 53 (9.43%)
         occurrences all number
    8

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Dec 2021
    Protocol Amendment 1: • Added a safety electrocardiogram (ECG) assessment 1-hour post dose at Cycle 1 Day 1 (C1D1) • Updated Gastric Acid Reducing Agents administration guidelines • Updated preferred terms for Reproductive System Disorders in the adverse events of special interest (AESI) table - Updated inclusion/exclusion criteria: Specified that participant must have had radiological evidence of relapse, and removed clinical relapse and increasing tumor markers as evidence of relapse - Added further detail regarding prior therapy - Removed life expectancy from inclusion criteria - Removed anticipated need for major surgical procedure from exclusion criteria - Removed placement of vascular access device from an exclusion criterion - Removed positive human immunodeficiency virus (HIV) infection and Hepatitis C infection as exclusion criteria - Removed Hepatitis B surface antigen at Screening from an exclusion criterion - Added duration of contraceptive use for women of childbearing potential (WOCBP)
    18 Jul 2022
    Protocol Amendment 2: • Changed serum creatinine (using the Cockcroft-Gault equation) to estimated glomerular filtration rate (eGFR) to better measure steady-state renal function
    31 Jan 2023
    Protocol Amendment 3: • Updated language regarding risks based on new information from Phase 3 study • Updated inclusion/exclusion criteria: - Reworded 2 inclusion criteria for accuracy − Revised exclusion criterion 11 regarding previous or current treatment for OvGCT to clarify use of bevacizumab or other monoclonal antibody therapy • Added guidance for selected toxicities not considered treatment-related and updated the list of selected toxicities • Updated duration of study to state the minimum duration • Updated laboratory assessments • Revised pregnancy information collection
    04 Jun 2023
    Protocol Amendment 4: • Added exploratory objective and endpoint • Updated estimated duration of the study • Updated study treatment duration parameters • Added scientific rationale and new guidance for continuation of treatment beyond initial evidence of disease progression • Added updated guidance for timing of co-administrating of acid reducing agents • Updated AESIs
    19 Mar 2024
    Protocol Amendment 5: • Added in assessment for continued use of nirogacestat following first disease progression • Added in analysis for progression free survival 2 (PFS2) • Additional text added to 2-year survival check-in to explain process for collection of PFS2 data • Duration of contraception and egg donation/harvesting shorted from 6 months to at least 1 week after the last dose of study treatment • Updated AESI table • Added additional text regarding reporting Suspected Unexpected Serious Adverse Reactions, data protection, and publication policy aligned with EU CTR requirements

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Aug 30 23:20:57 CEST 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA