Nirogacestat in Ovarian Granulosa Cell Tumors

• ClinicalTrials.gov Identifier: NCT05348356
• Recruitment Status: Active, not recruiting
• First Posted: April 27, 2022
• Last Update Posted: November 22, 2023
• Sponsor: SpringWorks Therapeutics, Inc.
• Information provided by (Responsible Party): SpringWorks Therapeutics, Inc.

Tracking Information

• First Submitted Date: April 13, 2022
• First Posted Date: April 27, 2022
• Last Update Posted Date: November 22, 2023
• Actual Study Start Date: August 30, 2022
• Estimated Primary Completion Date: July 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2022)

Objective Response Rate (ORR) [ Time Frame: 2.5 years ]

The proportion of participants with complete response (CR) + partial response (PR) assessed using RECIST v1.1 criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 20, 2022)

• 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. ]
  The number of participants without progression according to RECIST v1.1 or death at 6 months.
• Overall Survival [ Time Frame: 2 years after first dose of study treatment ]
  The number of participants who have not died of any cause.
• Participant reported ovarian cancer symptoms [ Time Frame: At each study visit until study completion (estimated to be an average of 2.5 years) ]
  Change from baseline as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI).
• 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). ]
  The time from response (CR + PR using RECIST v.1.) to disease progression and/or death

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nirogacestat in Ovarian Granulosa Cell Tumors
• Official Title: A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Ovarian Granulosa-Stromal Tumor
• Ovarian Granulosa Cell Tumor
• Ovarian Cancer

Intervention

Drug: Nirogacestat

nirogacestat oral tablet

Other Name: PF-03084014

Study Arms

Experimental: Nirogacestat Open-Label

All participants will receive open-label nirogacestat

Intervention: Drug: Nirogacestat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 7, 2023): 53
• Original Estimated Enrollment (submitted: April 20, 2022): 43
• Estimated Study Completion Date: December 2027
• Estimated Primary Completion Date: July 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• 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:

• 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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Poland, United States
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT05348356
• Other Study ID Numbers: NIR-OGT-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: SpringWorks Therapeutics is committed to data transparency and sharing data to further research while maintaining the privacy and confidentiality of research participants. Pertinent patient-level data from completed clinical trials will be made available by SpringWorks to qualified researchers upon approval of reasonable requests following de-identification/anonymization pursuant to applicable law.

• Current Responsible Party: SpringWorks Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: SpringWorks Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: SpringWorks Therapeutics, Inc.
• Verification Date: November 2023