Nirogacestat in Ovarian Granulosa Cell Tumors

NCT05348356 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: NIR-OGT-2012022-001816-25
• Study Type: interventional
• Target: 53
• Locations: 3 countries
• Sites: 21

Brief 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.

Conditions

Ovarian Granulosa-Stromal Tumor; Ovarian Granulosa Cell Tumor; Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  2.5 years

Secondary Outcomes (9)

• Progression Free Survival at 6 Months (PFS-6)

  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

  2 years after first dose of study treatment

• Duration of Response

  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.

  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

  Baseline and at Cycle 3 Day 1 (cycle length is 28 days).

Study Arms (1)

Nirogacestat Open-Label

EXPERIMENTAL

Nirogacestat 150 mg by mouth, twice daily Nirogacestat oral tablet: Nirogacestat tablet

Drug: Nirogacestat

Interventions

Nirogacestat DRUG

nirogacestat oral tablet

Also known as: PF-03084014

Nirogacestat Open-Label

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany: lead

Study Sites (21)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit

Los Angeles, California, 90095, United States

Location

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Women's Cancer Care

Covington, Louisiana, 70433, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

David C. Pratt Cancer Center

St Louis, Missouri, 63141, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Institute

New York, New York, 10065, United States

Location

Women's Cancer Center at Kettering

Kettering, Ohio, 45429, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

UW/Fred Hutch Cancer Center

Seattle, Washington, 98109, United States

Location

Froedtert and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Maria Sklodowska-Curie Bialystok Oncology Center

Bialystok, 15-027, Poland

Location

Jagiellonian Innovation Centre Clinical Research Centre

Krakow, 30-348, Poland

Location

University Teaching Hospital Poznan, Department of Oncological Gynaecology

Poznan, 60-569, Poland

Location

Maria Sklodowska-Curie National Institute of Oncology-National Research Institute, Clinic of Oncological Gynecology

Warsaw, 02-781, Poland

Location

Related Publications (1)

• 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.

  PMID: 41518037 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Granulosa cell tumor of the ovary; Ovarian Neoplasms

Interventions

nirogacestat

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

:+49-6151-72-5200

Study Officials

• Medical Responsible

  SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2022
• First Posted: April 27, 2022
• Study Start: August 30, 2022
• Primary Completion: July 8, 2025
• Study Completion: July 14, 2025
• Last Updated: August 25, 2026
• Results First Posted: August 25, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: IPD from completed trials will be publicly available within 6 months after all of the following events: * Approval of a product/new indication by major authorities (FDA, EMA, PMDA if requested) with no pending submissions * Public results via primary manuscript or trial registry disclosure * Legal authority to share data * Privacy protections are in place If approval is not sought or development is globally discontinued, data will be publicly available within 18 months after global trial completion. Further information on how to request data can be found on our website bit.ly/IPD21
• Access Criteria: Qualified researchers may propose access to IPD from sponsored trials via https://vivli.org/members/ourmembers/.

Locations

PL (4); US (16); CA (1)