Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors and in Phase 2 clinical development for ovarian granulosa cell tumors. ChemSpider ID 26232306. - Mechanism of Action & Protocol. The aim of the present study was to explore the feasibility and effectiveness of umbilical cord mesenchymal stem cell (UCMSC) transplantation for the treatment of POI in a rat model of POI induced by . Some genetic disorders are associated with primary ovarian insufficiency. Among important research news last week, US pharma giant Merck & Co released positive Phase III results for the pulmonary arterial . Full Title A Safety, Pharmacokinetic and Efficacy Study of a y-Secretase Inhibitor, Nirogacestat (PF-03084014, IND 146375), in Children and Adolescents with Progressive, Surgically Unresectable Desmoid Tumors (ARST1921) (CIRB) Purpose The purpose of this study is to assess the safety and effectiveness of the investigational drug nirogacestat in children and adolescents with desmoid tumors that . In the double-blind phase, half of the .. . Patient management. This can lead to infertility and a higher risk for other conditions. 4 Nirogacestat elicited an ORR of 29.4%, with no progressive. These include conditions in which you have one typical X chromosome and one altered X chromosome (mosaic Turner syndrome) and in which X chromosomes are fragile and break (fragile X syndrome). The Phase 2 trial (NCT05348356) is a multi-center, single-arm, open-label study evaluating the efficacy, tolerability, safety, and pharmacokinetics 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). doi: 10.1002/ctm2.1006. A pregnancy test is done, and serum FSH and estradiol levels are measured weekly for 2 to 4 weeks; if FSH levels are high ( > 20 mIU/mL, but usually > 30 mIU/mL) and estradiol levels are low . Lenvima plus Keytruda disappoints in unresectable hepatocellular cancer. As Dr. Cassidy explains, nirogacestat is an oral, selective, small molecule, gamma-secretase inhibitor. The POI condition is characterized by decline in ovarian function due to premature depletion of follicles that result in an earlier than average menopause affecting approximately 1%-2% of women under 40 years of age (Monniaux et al., 2014). The disease can be either asymptomatic or be associated with severe loss of . The estimated incidence is: by age 20: 1:10,000. by age 30: 1:1000. by age 35: 1:250. by age 40: 1:100. This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). A common cause of primary ovarian insufficiency in adolescents is gonadal dysgenesis, with or without Turner syndrome 3. ICH GCP. Women with POI present in primary care with menstrual . Different experimental approaches are being explored . National Cancer Institute. To determine the effectiveness of nirogacestat at 150mg twice a day in patients with ovarian granulosa cell tumors, the agent has been administered to the first patient in a phase 2 trial. Nirogacestat is being investigated for the treatment of desmoid tumors due to its ability to bind to GS, blocking proteolytic activation of Notch receptors. Gynecologic anomalies, including uterine agenesis and ovarian dysgenesis, are some of the several differential diagnoses in adolescent females with primary amenorrhea and delayed puberty. 12-09-2022. Kineta, a privately-held immuno-oncology company, has announced that it has entered into a clinical trial collaboration and supply agreement with Merck & Co. 1 Approximately one in 100 women aged < 40 years and one in . In women aged 40 years or older, the expected physiologic decline of ovarian function that takes place with aging is termed perimenopause or the menopausal transition. 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%). Heterogeneity of POI is registered by . . SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe MedKoo CAT#: 525757. We do not sell or distribute actual drugs. POI is not an early menopause. In the double-blind phase, half of the participants will receive nirogacestat while the other half will receive placebo. nirogacestat. The final analysis of the Phase III LEAP-002 trial investigating Lenvima (lenvatinib), discovered by Japan's Eisai plus US pharma giant Merck & Co's mega blockbuster Keytruda (pembrolizumab) versus Lenvima monotherapy, was inconclusive for the combination as first-line treatment for patients with . Premature ovarian insufficiency (POI) is a hypergonadotropic hypogonadism condition which is characterised by impairment of ovarian function on a continuum before the age of 40 years. The study will enroll approximately 40 patients who will receive 150mg of nirogacestat twice daily. symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic . Background:-Desmoid tumors (also known as aggressive fibromatosis), are rare, locally invasive, slow-growing soft-tissue tumors. Molecular Formula CHFNO. This age limit of 40 years has been taken as the cut-off age for POI as this age is approximately two standard deviations below the natural age of menopause. . Primary ovarian insufficiency is when the ovaries lose function before age 40. When adolescents present with primary amenorrhea and no associated comorbidities, 50% are found to have abnormal karyotypes. Primary ovarian insufficiency is primarily idiopathic, but it can also be seen in association with chromosomal and genetic defects, including Turner syndrome (45,X . Intervention(s) Drug: PF-03084014. 1 It is characterised by menstrual irregularities (infrequent menstrual cycles or amenorrhoea) with elevated FSH and LH levels and low oestradiol levels. Email: intl.mcr@mayo.edu. Toxins. Many women naturally experience reduced fertility when they are about 40 years old. Ovarian Cancer / Ovarian Granulosa Cell Tumor / Ovarian Granulosa-Stromal Tumor: 1: 2: Ovary Insufficiency. Primary ovarian insufficiency may be caused by: Chromosome changes. In women with this condition, the ovaries (organs that produce a woman's eggs) stop producing eggs before age 40. Metabolic dysregulation in patients with premature ovarian insufficiency revealed by integrated transcriptomic, methylomic and metabolomic analyses Clin Transl Med . Nirogacestat enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Background. Primary ovarian insufficiency (POI), also known as premature ovarian failure, happens when a woman's ovaries stop working normally before she is 40. Cancer-related trials contact form. Nirogacestat has been used in trials studying the treatment of Breast Cancer, HIV Infection, . Typical symptoms found when the menopause occurs later, such as hot flushes and night sweats, may not be present. Supporting Site. . Primary ovarian insufficiency (POI) is a disease spectrum that not only affects female fertility but also contributes to morbidity and mortality associated with the long-term withdrawal of estrogen. Build, train, & validate machine-learning models with evidence-based and structured datasets. Premature ovarian insufficiency (POI) is an ovarian insufficiency syndrome before the age of 40 years affecting approximately 1-2% women [26, 12].It is characterized by a continuous decline in ovarian function, and resulting in an earlier cessation of menstruation than normal [].Women with POI are faced with increased risk of low chance of natural conception [4, 38], urogenital atrophy . In the case of ovarian cancer, . Ovarian insufficiency is a failure of the ovary to function adequately in a woman younger than 40 years, in its role either as an endocrine organ or as a reproductive organ. Nirogacestat (PF-03084014) is a potent, small molecule, selective, reversible, noncompetitive inhibitor of -secretase (GS) with a potential antitumor activity. Final gross price and currency may vary according to local VAT and billing address. 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%). - 2 of 2 defined stereocentres. CAS#: 1290543-63-3 (free base) Description: Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. Nirogacestat (PF-3084014) is a tetralin imidazole gamma-secretase inhibitor. Find out more about your treatment options, how . The majority of women with childbearing potential had adverse events (AEs) consistent with ovarian dysfunction and other AEs were generally consistent with previously reported data. It was granted FDA breakthrough drug designation in September 2019 for adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. Reduce drug development failure rates. Gamma-secretase, a proteolytic enzyme complex, mediates processing of several integral membrane proteins including amyloid precursor protein and Notch. - Participant has an abnormal QT interval at screening. Stem cell therapy is expected to be used in the treatment of POI. Nirogacestat | C27H41F2N5O | CID 46224413 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities . Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers. Nirogacestat was generally well tolerated with a manageable safety profile. Trial Description: This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). They may start getting irregular menstrual periods as they transition to menopause. Primary ovarian insufficiency (POI) is a condition resulting from the depletion or dysfunction of the ovarian follicles, leading to cessation of ovulation and menses before age 40. POI is associated with cardiovascular morbidity, osteoporosis and premature mortality. The FDA has granted nirogacestat (PF-03084014), an investigational gamma-secretase inhibitor, with a breakthrough therapy designation for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. (Nirogacestat) has spurred the phase III trial in adult patients with desmoid tumors (NCT03785964), recent breakthrough designation by the U.S. Food and Drug Administration, and orphan drug designation by the European Commission. September 4, 2019. Premature ovarian insufficiency (POI) occurs in women aged under 40 years and is a syndrome consisting of amenorrhoea, elevated gonadotrophins and oestrogen deficiency. Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. Eligibility Requirements: It is biochemically characterized by amenorrhea with hypoestrogenic and hypergonadotropic conditions, in some cases, causing loss of fertility. Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation. Primary ovarian insufficiency is suspected in women < 40 with unexplained infertility, menstrual abnormalities, or symptoms of estrogen deficiency. This compound can inhibit both Notch-related pathway in neoplasia and reduces amyloid- production. [2] 2022 Oct;12(10):e1006. About the Phase 2 Trial of Nirogacestat Trial Name: Nirogacestat in Ovarian Granulosa Cell Tumors ClinicalTrials.gov Indentifier: NCT05348356 Premature ovarian insufficiency (POI) or premature ovarian failure (POF) is known as a state of hypergonadotropic hypogonadism. This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors. Monoisotopic mass 489.327911 Da. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which may contribute to desmoid tumor growth. This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). Bone Loss and Fracture Risk. STAMFORD, Conn., Sept. 29, 2022 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (NASDAQ:SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for . Primary ovarian insufficiency is suspected in women < 40 with unexplained infertility, menstrual abnormalities, or symptoms of estrogen deficiency. Average mass 489.644 Da. Lisa Astor. Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.. Clinical Trials Registry. Infertility: The majority of individuals with primary ovarian insufficiency experience infertility and require medical intervention to become pregnant. The FDA has granted a breakthrough therapy designation to the investigational gamma-secretase inhibitor nirogacestat (PF-03084014) for the treatment of adult . PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. Premature ovarian insufficiency (POI) is a disease char-acterized by oligomenorrhea, hypoestrogenism and a folli-cle-stimulating hormone (FSH) level higher than 25 IU/L that occurs in women younger than 40 years of age [1,2]. Primary (or premature) ovarian insufficiency * is a clinical syndrome defined by the loss of ovarian function before the age of 40 years. Women with primary ovarian insufficiency-related estrogen deficiency are at risk of osteopenia, osteoporosis, and fracture, especially if hypoestrogenism occurs early in life and before accrual of peak bone mass 3 12 13 14.In studies that have evaluated the role of HT in women at elevated risk of fracture based on menopausal age, significant reductions in fracture . Heart disease: When estrogen levels are low, cholesterol is more likely to build up in the . Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective -secretase inhibitor with an IC50 of 6.2 nM. The Phase 2 trial ( NCT05348356) is a multi-center, single-arm, open-label study evaluating the efficacy, tolerability, safety, and pharmacokinetics of nirogacestat in patients with recurrent. Primary ovarian insufficiency is a disorder that occurs when a woman's ovaries stop functioning prematurely (earlier than normal). Nirogacestat is an investigational oral, selective, small molecule gamma secretase inhibitor (GSI) in Phase 3 clinical development for adult patients with progressing desmoid tumors and in Phase 2 clinical development for patients with ovarian granulosa cell tumors. Share this article. Failure as a monotherapy has spurred combinatorial regimens. Among younger women (aged 30 years or younger) with secondary amenorrhea, 13% also have been noted . Primary ovarian insufficiency is suspected in women < 40 with unexplained infertility, menstrual abnormalities, or symptoms of estrogen deficiency. Nirogacestat, a selective gamma-secretase inhibitor, has been investigated in 24 patients with desmoid tumors across Phase 1 and Phase 2 studies; the Company is planning a Phase 3 study (DeFi . Protocol Number Title Protocol Status Min-Max Age Institute Keywords: 000760-H: Extension Study (extended access) of Syk-inhibition Using Fostamatinib to Treat Post-Transplant Immune-mediated Cytopenias However, this terminology has fallen out of favor as the degree . It has been suggested that POI may affect 1% of women under 40 [1,3,4]. symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. The usual age for egg production to stop, known as menopause, is around 50. The purpose of this study is to assess the safety and toxicity of ABBV-383 when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd), or nirogacestat (Niro) in adult participants with relapsed/refractory (R/R . The Phase 2 trial (NCT05348356) is a multi-center, single-arm, open-label study evaluating the efficacy, tolerability, safety, and pharmacokinetics of nirogacestat in patients with recurrent ovarian granulosa cell tumors. Nirogacestat - SpringWorks Therapeutics Alternative Names: Nirogacestat hydrobromide; PF 3084014; PF-03084014; PF-03084014-04 Latest Information Update: 04 Oct 2022 Price : $50 * Buy Profile Adis is an information provider. The Phase 2 trial (NCT05348356) is a multi-center, single-arm, open-label study evaluating the efficacy, tolerability, safety, and pharmacokinetics of nirogacestat in patients with recurrent . View Full Description Full Description Phone: 507-284-8884. Premature ovarian insufficiency is a common disorder affecting young women and represents the worst-case ovarian scenario due to the substantial impact on the reproductive lifespan of these patients. Phone: 855-776-0015 (toll-free) International patient clinical studies questions. Again, the median PFS had not yet been reached at the time of the publication data because of a lack of tumor progression events. ; Osteoporosis: Estrogen is a hormone that keeps bones dense and strong.Without an adequate supply, the bones weaken and are more likely to break. Due to the complexity of this condition, which is not fully understood, non-effective treatments have yet been established for these patients. The abnormalities of bone resorption may induce a series of diseases, including osteoarthritis, osteoporosis and aseptic peri-implant loosening. A pregnancy test is done, and serum FSH and estradiol levels are measured weekly for 2 to 4 weeks; if FSH levels are high ( > 20 mIU/mL, but usually > 30 mIU/mL) and estradiol levels are low . Premature ovarian insufficiency (POI), defined as amenorrhoea due to the loss of ovarian function before 40 years of age, can occur spontaneously or be secondary to medical therapies. Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors. 1 The breakthrough designation was granted as a result of positive findings seen in phase I and II trials of nirogacestat monotherapy . Primary ovarian insufficiency: an overview. Primary ovarian insufficiency is reported in the clinical practice of reproductive endocrinology can be determined by conducting sex hormone tests to evaluate the hypothalamic-pituitary-ovarian axis. Notably, most individuals capable of bearing children experienced an adverse effect that was consistent with ovarian dysfunction, although most toxicities were consistent with previously reported findings. Ovarian insufficiency occurs in approximately 1% of women. Nirogacestat (PF-03084014) Investigational Device(s) None . Copied . September 29, 2022, 10:30 AM UTC. A pregnancy test is done, and serum FSH and estradiol levels are measured weekly for 2 to 4 weeks; if FSH levels are high ( > 20 mIU/mL, but usually > 30 mIU/mL) and estradiol levels are low . In terms of safety, nirogacestat had a manageable safety profile and was well tolerated. Nirogacestat ( PF-03084014) is a selective gamma secretase inhibitor [1] developed by SpringWorks Therapeutics that has potential anti-tumor activity. SpringWorks Therapeutics Announces Dosing of First Patient in Phase 2 Trial Evaluating Nirogacestat in Patients with Ovarian. Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. This disease spectrum has previously been referred to as premature ovarian failure. Premature ovarian insufficiency (POI) is the loss of normal ovarian function before the age of 40 years, a condition that affects approximately 1% of women under 40 years old and 0.1% of women under 30 years old. Nirogacestat enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation. There are currently two active clinical trials of nirogacestat as a treatment for Desmoid tumors. The study will enroll approximately 40 patients who will receive 150mg of nirogacestat twice daily.
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