A Phase 2 interventional study of Nirogacestat in Ovarian Granulosa-Stromal Tumor, Ovarian Granulosa Cell Tumor and Ovarian Cancer, sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany. Completed at 21 sites in 3 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany · Phase 2, Interventional, and Treatment
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.
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.
Key Inclusion Criteria:
Key Exclusion Criteria:
Nirogacestat 150 mg by mouth, twice daily Nirogacestat oral tablet: Nirogacestat tablet
Drug: Nirogacestat
nirogacestat oral tablet
Also known as: PF-03084014
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.
Time frame: 2.5 years
Progression Free Survival at 6 Months (PFS-6)
The number of participants without progression according to RECIST v1.1 or death at 6 months.
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
The number of participants who have not died of any cause by Year 2.
Time frame: 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.
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.
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.
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
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.
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
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.
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
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.
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
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.
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
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.
Time frame: Baseline and at safety follow-up (up to a maximum of 34 months).
| Milestone | Nirogacestat Open-Label |
|---|---|
| Started | 53 |
| Completed | 1 |
| Not completed | 52 |
| Withdrew: Death | 1 |
| Withdrew: Lack of efficacy | 38 |
| Withdrew: Withdrawal by subject | 4 |
| Withdrew: Physician decision | 8 |
| Withdrew: Clinical progression | 1 |
The percentage of participants with complete response (CR) + partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
| percentage of participants | Nirogacestat Open-Label |
|---|---|
| Objective Response Rate (ORR) | 0 |
The number of participants without progression according to RECIST v1.1 or death at 6 months.
| Participants | Nirogacestat Open-Label |
|---|---|
| Progression Free Survival at 6 Months (PFS-6) | 22 |
The number of participants who have not died of any cause by Year 2.
| Participants | Nirogacestat Open-Label |
|---|---|
| Overall Survival at Year 2 | 47 |
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.
No measurements were reported for this outcome.
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.
| score on a scale | Nirogacestat Open-Label |
|---|---|
| Change From Baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score. | -1.1 ± 3.86 |
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.
| score on a scale | Nirogacestat Open-Label |
|---|---|
| Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score | -1.2 ± 4.00 |
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.
| score on a scale | Nirogacestat Open-Label |
|---|---|
| Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score | -1.5 ± 3.08 |
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.
| score on a scale | Nirogacestat Open-Label |
|---|---|
| Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score | -1.3 ± 3.36 |
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.
| score on a scale | Nirogacestat Open-Label |
|---|---|
| Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score | -2.2 ± 4.48 |
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.
| score on a scale | Nirogacestat Open-Label |
|---|---|
| Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score | -0.8 ± 3.75 |
Collected over 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).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Nirogacestat Open-Label | 7/53 (13.2%) | 12/53 (22.6%) | 52/53 (98.1%) |
| Event | Nirogacestat Open-Label |
|---|---|
| Abdominal painGastrointestinal disorders | 4/53 |
| Acute kidney injuryRenal and urinary disorders | 2/53 |
| DehydrationMetabolism and nutrition disorders | 2/53 |
| DiarrhoeaGastrointestinal disorders | 2/53 |
| HypokalaemiaMetabolism and nutrition disorders | 2/53 |
| Small intestinal obstructionGastrointestinal disorders | 2/53 |
| Acute myocardial infarctionCardiac disorders | 1/53 |
| Angina pectorisCardiac disorders | 1/53 |
| Cardio-respiratory arrestCardiac disorders | 1/53 |
| ColitisGastrointestinal disorders | 1/53 |
| Event | Nirogacestat Open-Label |
|---|---|
| DiarrhoeaGastrointestinal disorders | 38/53 |
| NauseaGastrointestinal disorders | 30/53 |
| FatigueGeneral disorders | 21/53 |
| VomitingGastrointestinal disorders | 20/53 |
| CoughRespiratory, thoracic and mediastinal disorders | 17/53 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 17/53 |
| HypophosphataemiaMetabolism and nutrition disorders | 15/53 |
| Abdominal painGastrointestinal disorders | 11/53 |
| HypokalaemiaMetabolism and nutrition disorders | 10/53 |
| EpistaxisRespiratory, thoracic and mediastinal disorders | 8/53 |
Full Analysis Set which consisted of of all participants who received at least 1 dose of nirogacestat.
| Age, Continuous(years) | Nirogacestat Open-Label |
|---|---|
| Mean | 55.1 ± 12.85 |
| Age, Customized(Participants) | Nirogacestat Open-Label |
|---|---|
| <45 years | 13 |
| >=45 years | 40 |
| Sex: Female, Male(Participants) | Nirogacestat Open-Label |
|---|---|
| Female | 53 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | Nirogacestat Open-Label |
|---|---|
| Hispanic or Latino | 6 |
| Not Hispanic or Latino | 43 |
| Unknown or Not Reported | 4 |
| Race (NIH/OMB)(Participants) | Nirogacestat Open-Label |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 3 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 37 |
| More than one race | 2 |
| Unknown or Not Reported | 7 |
| Region of Enrollment(Participants) | Nirogacestat Open-Label |
|---|---|
| United States | 50 |
| Poland | 3 |
| Baseline Weight(kilogram) | Nirogacestat Open-Label |
|---|---|
| Mean | 82.48 ± 19.672 |
| Baseline Height(meter) | Nirogacestat Open-Label |
|---|---|
| Mean | 1.632 ± 0.0611 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — IPD supporting publicly available results will be evaluated for sharing.
Supporting information: Study protocol, Sap, Csr, Analytic code
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Granulosa cell tumor of the ovary
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany