nirogacestat. Copied 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 . 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 . Trial Description: This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). 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. It is biochemically characterized by amenorrhea with hypoestrogenic and hypergonadotropic conditions, in some cases, causing loss of fertility. 2022 Oct;12(10):e1006. 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 . In terms of safety, nirogacestat had a manageable safety profile and was well tolerated. 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. Primary ovarian insufficiency is suspected in women < 40 with unexplained infertility, menstrual abnormalities, or symptoms of estrogen deficiency. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. 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. Monoisotopic mass 489.327911 Da. 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. 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 . 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. View Full Description Full Description . Gamma-secretase, a proteolytic enzyme complex, mediates processing of several integral membrane proteins including amyloid precursor protein and Notch. The FDA has granted a breakthrough therapy designation to the investigational gamma-secretase inhibitor nirogacestat (PF-03084014) for the treatment of adult . This disease spectrum has previously been referred to as premature ovarian failure. Nirogacestat is being investigated for the treatment of desmoid tumors due to its ability to bind to GS, blocking proteolytic activation of Notch receptors. Due to the complexity of this condition, which is not fully understood, non-effective treatments have yet been established for these patients. 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. It has been suggested that POI may affect 1% of women under 40 [1,3,4]. This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). 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. National Cancer Institute. Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.. Clinical Trials Registry. Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors. Background. Kineta, a privately-held immuno-oncology company, has announced that it has entered into a clinical trial collaboration and supply agreement with Merck & Co. Lenvima plus Keytruda disappoints in unresectable hepatocellular cancer. - Mechanism of Action & Protocol. Average mass 489.644 Da. This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Among important research news last week, US pharma giant Merck & Co released positive Phase III results for the pulmonary arterial . Supporting Site. Find out more about your treatment options, how . Toxins. Patient management. symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. Stem cell therapy is expected to be used in the treatment of POI. Primary ovarian insufficiency is when the ovaries lose function before age 40. Phone: 507-284-8884. . 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. Failure as a monotherapy has spurred combinatorial regimens. In women with this condition, the ovaries (organs that produce a woman's eggs) stop producing eggs before age 40. There are currently two active clinical trials of nirogacestat as a treatment for Desmoid tumors. 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 . 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 As Dr. Cassidy explains, nirogacestat is an oral, selective, small molecule, gamma-secretase inhibitor. 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. symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic . Eligibility Requirements: Nirogacestat (PF-3084014) is a tetralin imidazole gamma-secretase inhibitor. This can lead to infertility and a higher risk for other conditions. Phone: 855-776-0015 (toll-free) International patient clinical studies questions. Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation. Nirogacestat was generally well tolerated with a manageable safety profile. September 4, 2019. Nirogacestat has been used in trials studying the treatment of Breast Cancer, HIV Infection, . 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 . The usual age for egg production to stop, known as menopause, is around 50. 1 It is characterised by menstrual irregularities (infrequent menstrual cycles or amenorrhoea) with elevated FSH and LH levels and low oestradiol levels. 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%). Primary ovarian insufficiency is a disorder that occurs when a woman's ovaries stop functioning prematurely (earlier than normal). 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. 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. 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. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which may contribute to desmoid tumor growth. This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). - 2 of 2 defined stereocentres. 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 . Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. Premature ovarian insufficiency (POI) occurs in women aged under 40 years and is a syndrome consisting of amenorrhoea, elevated gonadotrophins and oestrogen deficiency. 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. Primary ovarian insufficiency is suspected in women < 40 with unexplained infertility, menstrual abnormalities, or symptoms of estrogen deficiency. ICH GCP. Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation. ChemSpider ID 26232306. Nirogacestat (PF-03084014) is a potent, small molecule, selective, reversible, noncompetitive inhibitor of -secretase (GS) with a potential antitumor activity. They may start getting irregular menstrual periods as they transition to menopause. Infertility: The majority of individuals with primary ovarian insufficiency experience infertility and require medical intervention to become pregnant. Nirogacestat ( PF-03084014) is a selective gamma secretase inhibitor [1] developed by SpringWorks Therapeutics that has potential anti-tumor activity. 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 . Share this article. Primary ovarian insufficiency (POI), also known as premature ovarian failure, happens when a woman's ovaries stop working normally before she is 40. Some genetic disorders are associated with primary ovarian insufficiency. A common cause of primary ovarian insufficiency in adolescents is gonadal dysgenesis, with or without Turner syndrome 3. 4 Nirogacestat elicited an ORR of 29.4%, with no progressive. SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe Email: intl.mcr@mayo.edu. Build, train, & validate machine-learning models with evidence-based and structured datasets. Different experimental approaches are being explored . 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. Molecular Formula CHFNO. Ovarian insufficiency occurs in approximately 1% of women. 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 . POI is associated with cardiovascular morbidity, osteoporosis and premature mortality. Primary ovarian insufficiency: an overview. Primary ovarian insufficiency may be caused by: Chromosome changes. 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. Primary (or premature) ovarian insufficiency * is a clinical syndrome defined by the loss of ovarian function before the age of 40 years. 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%). 1 Approximately one in 100 women aged < 40 years and one in . When adolescents present with primary amenorrhea and no associated comorbidities, 50% are found to have abnormal karyotypes. We do not sell or distribute actual drugs. 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 . 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