A Phase 4 interventional study of Nirogacestat in Desmoid Tumor and Aggressive Fibromatosis, sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany. Recruiting at 23 sites in 6 countries. Open to female participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany · Phase 4, Interventional, and Treatment
This study is being conducted to study how nirogacestat may affect the ovarian function of adult premenopausal women with progressing desmoid tumors/aggressive fibromatosis.
Desmoid tumors, also referred to as aggressive fibromatosis, are rare, locally invasive, slow growing soft tissue tumors. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and occasionally mortality in patients.
Nirogacestat is a tumor inhibitor that works by slowing or stopping the growth of tumor cells. Nirogacestat is a tablet taken by mouth and has been approved in the USA for adult patients with progressing desmoid tumors who require systemic treatment.
This is an open-label study to characterize the incidence and ovarian function recovery rates of ovarian toxicity (OT) events and to evaluate the efficacy, safety, and tolerability of nirogacestat in postpubertal and premenopausal females with desmoid tumors (DT).
Exclusion Criteria:
Nirogacestat 150 mg by mouth, twice daily
Drug: Nirogacestat
Nirogacestat oral tablet
Also known as: PF-03084014, Ogsiveo
Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs)
Ovarian function recovery is defined as achieving the resumption of ≥2 consecutive menstrual periods and an FSH level \<30 mIU/mL with concomitant estradiol \<80 pg/mL OR resumption of ≥2 consecutive menstrual periods and AMH level within normal range adjusted for age and pretreatment baseline OR a positive serum β-HCG pregnancy test.
Time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
Incidence of OT TEAEs
OT is any new onset amenorrhea lasting ≥3 consecutive menstrual periods, FSH level ≥30 mIU/mL and a negative β-HCG pregnancy test.
Time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
Time to ovarian function recovery in participants with a TEAE of OT
Time to ovarian function recovery is evaluated in participants who had a TEAE of OT and is defined as the time it takes to resolve.
Time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
The incidence of adverse events (AEs) according to toxicities graded by National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) Version 5
Time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
Objective Response Rate (ORR)
Proportion of participants with Complete Response (CR) and Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
Time frame: First day of every 3 cycles (each cycle is 28 days) for up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period
Duration of Response (DoR) for participants whose best response is CR or PR
DoR is defined as the duration from the time of first assessment of CR or PR response (per RECIST v1.1) to the first date of disease progression or death (whichever comes first).
Time frame: First day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period
Disease Control Rate (DCR) for participants whose best response is CR, PR or Stable Disease (SD)
DCR is defined as the proportion of participants who have a best response of CR, PR, or SD.
Time frame: First day of every 3 cycles (each cycle is 28 days) for up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period
Duration of Disease Control (DoDC) for participants whose best response is CR, PR or SD
DoDC is defined as the duration from the start of study treatment until first date of disease progression or death (whichever comes first).
Time frame: First day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period
Progression Free Survival (PFS)
PFS is defined at the start of study treatment until the date of assessment of progression or death by any cause. Progression will be determined radiographically using RESIST v1.1 performed by a local radiologist.
Time frame: First day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period
Changes in tumor volume from baseline assessed by MRI volumetric analysis performed locally
Time frame: First day of every 3 cycles (each cycle is 28 days) up to 24 cycles and up to 1 year in the Clinical Follow-up Period
Change in T2 hyperintensity baseline assessed by MRI analysis performed locally
Time frame: First day of every 3 cycles (each cycle is 28 days) up to 24 cycles and up to 1 year in the Clinical Follow-up Period
Characterization of serum nirogacestat concentrations assessed in sparse pharmacokinetic (PK) sampling (pre-dose and 1-hour post dose at Cycle 1 Day 1 only) and trough PK sampling (pre-dose at treatment period visits after Cycle 1 Day 1
Time frame: First day of every 3 cycles (each cycle is 28 days) up to 24 cycles of treatment
Pain severity using Brief Pain Index - Short Form (BPI-SF), question #3
BPI question #3 will measure worst pain in the last 24 hours using an 11-point numeric scale from 0 (no pain) to 10 (pain as bad as you can imagine)
Time frame: From 7 days prior to date of first dose of treatment through end of Cycle 2 (each cycle is 28 days), assessed up to 9 weeks
Patient experience of desmoid tumors and nirogacestat
Two (2) optional 60-minute qualitative interviews using open-ended exploratory questions to elicit spontaneous responses will be transcribed and analyzed in an inductive/deductive method to identify themes in the data
Time frame: One interview will occur following treatment completion (on average approximately 2 years after study entry) and a second interview will occur at study completion (on average approximately 3 years after study entry)
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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SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany