Ovarian Granulosa-Stromal TumorPhase 2NCT05348356
Nirogacestat in Ovarian Granulosa Cell Tumors
A Phase 2 study testing Nirogacestat in people with Ovarian Granulosa-Stromal Tumor and Ovarian Granulosa Cell Tumor, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 21 sites in 3 countries.
Trial summary
This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Granulosa-Stromal Tumor, Ovarian Granulosa Cell Tumor, Ovarian Cancer
- What is being tested?
- Nirogacestat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 30 Aug 2022to 14 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has histologically confirmed recurrent adult-type granulosa cell tumor of the ovary prior to first dose of study treatment
- Have documented radiological evidence of relapse after at least one systemic therapy that is not amenable to surgery, or radiation and have measurable disease by RECIST v1.1 criteria
- Have adequate bone marrow, renal and hepatic function as defined by screening visit laboratory values
Who cannot join
- Has signs of bowel obstruction requiring parenteral nutrition, malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat
- Has had a major cardiac or thrombo-embolic event within 6 months of signing informed consent
- Has abnormal QT interval at Screening, or has congenital or acquired long QT syndrome or a history of additional risk factors for Torsades de Pointes
- Has current or chronic history of liver disease or known hepatic or biliary abnormalities
- Has received bevacizumab treatment or other monoclonal antibody therapy with targeted anti-angiogenic activity for OvGCT within 28 days (or 5 half-lives, whichever is shorter) prior to the first dose of study treatment;
- Has received treatment for OvGCT including but not limited to the following within 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment: hormonal therapy, chemotherapy, immunotherapy, targeted therapy or any investigational treatment
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
United States16 sites
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87102
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Women's Cancer Care
Covington, Louisiana, 70433
Women's Cancer Center at Kettering
Kettering, Ohio, 45429
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit
Los Angeles, California, 90095
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Institute
New York, New York, 10065
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
AdventHealth Orlando
Orlando, Florida, 32804
Orlando Health Cancer Institute
Orlando, Florida, 32806
UW/Fred Hutch Cancer Center
Seattle, Washington, 98109
David C. Pratt Cancer Center
St Louis, Missouri, 63141
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Poland4 sites
Maria Sklodowska-Curie Bialystok Oncology Center
Bialystok, 15-027
Jagiellonian Innovation Centre Clinical Research Centre
Krakow, 30-348
University Teaching Hospital Poznan, Department of Oncological Gynaecology
Poznan, 60-569
Maria Sklodowska-Curie National Institute of Oncology-National Research Institute, Clinic of Oncological Gynecology
Warsaw, 02-781
About this study
Official title: A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors
This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.
Read the detailed description
Ovarian granulosa cell tumors (OvGCTs) represent 5-7% of all ovarian cancers (~1.5 to 2k newly diagnosed patients/year in the United States) and are the most common subtype of ovarian sex cord tumors (70%). Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation.
This is a multi-center, single-arm, Phase 2 open label treatment study to determine the efficacy, safety, tolerability, and pharmacokinetics of nirogacestat in adult participants with relapsed/refractory OvGCT. The participants will continue treatment until disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (unless the participants meet criteria for continued treatment) or unacceptable toxicity.
- Being tested
- Nirogacestat
- Medical subject headings
- Granulosa cell tumor of the ovary, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NirogacestatDrug
Also called PF-03084014
nirogacestat oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Nirogacestat Open-Label | Experimental | Nirogacestat 150 mg by mouth, twice daily
Nirogacestat oral tablet: Nirogacestat tablet Receives: Drug: Nirogacestat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The percentage of participants with complete response (CR) + partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Measured: 2.5 years
Secondary outcomes (9)
Progression Free Survival at 6 Months (PFS-6)
The number of participants without progression according to RECIST v1.1 or death at 6 months.
Measured: First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days.
Overall Survival at Year 2
The number of participants who have not died of any cause by Year 2.
Measured: 2 years after first dose of study treatment
Duration of Response
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.
Measured: 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).
Change From Baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.
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.
Measured: Baseline and at Cycle 2 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
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.
Measured: Baseline and at Cycle 3 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
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.
Measured: Baseline and at Cycle 4 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
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.
Measured: Baseline and at Cycle 5 Day 1 (cycle length is 28 days).
Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
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.
Measured: Baseline and at end of treatment (estimated to be an average of 5.5 months [minimum of 0 month and maximum of 33 months]).
Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
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.
Measured: Baseline and at safety follow-up (up to a maximum of 34 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2022
- Study start30 Aug 2022
- Primary completion8 Jul 2025
- Study completion14 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian Granulosa-Stromal TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05348356
- Sponsor's protocol ID
- NIR-OGT-201
- Other IDs
- 2022-001816-25
- Status last verified
- Jul 2026
- First submitted
- 13 Apr 2022
- Last updated
- 25 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD supporting publicly available results will be evaluated for sharing.
Publications
Grisham RN, Hopp E, Pennington K, Holloway R, Wenham RM, Blecharz P, Dockery L, Matsuo K, Salani R, Bidzinski M, Braly P, Celano P, Reid T, Seward S, Lewis J, Johnson M, DuBose R, Ahn S, Cheng S, Alvero C, Konstantinopoulos PA. Phase II clinical trial of nirogacestat in patients with relapsed ovarian granulosa cell tumours. Clin Transl Med. 2026 Jan;16(1):e70568. doi: 10.1002/ctm2.70568.
PubMed 41518037
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors
- ClinicalTrials.gov ID
- NCT05348356
- Acronym / sponsor ID
- NIR-OGT-201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 30 Aug 2022 (actual)
- Primary completion
- 8 Jul 2025 (actual)
- Study completion
- 14 Jul 2025 (actual)
- First posted
- 27 Apr 2022 (actual)
- Results
- Posted 25 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.
Detailed description
Ovarian granulosa cell tumors (OvGCTs) represent 5-7% of all ovarian cancers (~1.5 to 2k newly diagnosed patients/year in the United States) and are the most common subtype of ovarian sex cord tumors (70%). Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation.
This is a multi-center, single-arm, Phase 2 open label treatment study to determine the efficacy, safety, tolerability, and pharmacokinetics of nirogacestat in adult participants with relapsed/refractory OvGCT. The participants will continue treatment until disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (unless the participants meet criteria for continued treatment) or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nirogacestat Open-Label | Experimental | Drug: NirogacestatNirogacestat 150 mg by mouth, twice daily Nirogacestat oral tablet: Nirogacestat tablet |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Has histologically confirmed recurrent adult-type granulosa cell tumor of the ovary prior to first dose of study treatment
- Have documented radiological evidence of relapse after at least one systemic therapy that is not amenable to surgery, or radiation and have measurable disease by RECIST v1.1 criteria
- Have adequate bone marrow, renal and hepatic function as defined by screening visit laboratory values
Key exclusion criteria (6 listed)
- Has signs of bowel obstruction requiring parenteral nutrition, malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat
- Has had a major cardiac or thrombo-embolic event within 6 months of signing informed consent
- Has abnormal QT interval at Screening, or has congenital or acquired long QT syndrome or a history of additional risk factors for Torsades de Pointes
- Has current or chronic history of liver disease or known hepatic or biliary abnormalities
- Has received bevacizumab treatment or other monoclonal antibody therapy with targeted anti-angiogenic activity for OvGCT within 28 days (or 5 half-lives, whichever is shorter) prior to the first dose of study treatment;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NirogacestatAlso: PF-03084014nirogacestat oral tablet | Drug | Nirogacestat Open-Label |
Primary outcome
Objective Response Rate (ORR)
Time frame: 2.5 years
The percentage of participants with complete response (CR) + partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
9 secondary outcomes
Progression Free Survival at 6 Months (PFS-6)
Time frame: First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days.
Overall Survival at Year 2
Time frame: 2 years after first dose of study treatment
Duration of Response
Time frame: 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).
Change From Baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.
Time frame: Baseline and at Cycle 2 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Time frame: Baseline and at Cycle 3 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Time frame: Baseline and at Cycle 4 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Time frame: Baseline and at Cycle 5 Day 1 (cycle length is 28 days).
Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Time frame: Baseline and at end of treatment (estimated to be an average of 5.5 months [minimum of 0 month and maximum of 33 months]).
Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Time frame: Baseline and at safety follow-up (up to a maximum of 34 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41518037Grisham RN, Hopp E, Pennington K, Holloway R, Wenham RM, Blecharz P, Dockery L, Matsuo K, Salani R, Bidzinski M, Braly P, Celano P, Reid T, Seward S, Lewis J, Johnson M, DuBose R, Ahn S, Cheng S, Alvero C, Konstantinopoulos PA. Phase II clinical trial of nirogacestat in patients with relapsed ovarian granulosa cell tumours. Clin Transl Med. 2026 Jan;16(1):e70568. doi: 10.1002/ctm2.70568.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- US Medical Information website, Medical ResourcesLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD supporting publicly available results will be evaluated for sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
21 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nirogacestat in people with Ovarian Granulosa-Stromal Tumor and Ovarian Granulosa Cell Tumor, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 21 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Poland, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05348356, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.