Molecular Formula CHFNO. SpringWorks Therapeutics Announces Dosing of First Patient in Phase 2 Trial Evaluating Nirogacestat in Patients with Ovarian. Primary ovarian insufficiency is when the ovaries lose function before age 40. ; Osteoporosis: Estrogen is a hormone that keeps bones dense and strong.Without an adequate supply, the bones weaken and are more likely to break. Lenvima plus Keytruda disappoints in unresectable hepatocellular cancer. STAMFORD, Conn., Sept. 29, 2022 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (NASDAQ:SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for . In terms of safety, nirogacestat had a manageable safety profile and was well tolerated. Cancer-related trials contact form. 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 . 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. 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. We do not sell or distribute actual drugs. This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). 1 Approximately one in 100 women aged < 40 years and one in . This can lead to infertility and a higher risk for other conditions. Heterogeneity of POI is registered by . Infertility: The majority of individuals with primary ovarian insufficiency experience infertility and require medical intervention to become pregnant. Heart disease: When estrogen levels are low, cholesterol is more likely to build up in the . Nirogacestat enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Metabolic dysregulation in patients with premature ovarian insufficiency revealed by integrated transcriptomic, methylomic and metabolomic analyses Clin Transl Med . 12-09-2022. Toxins. The abnormalities of bone resorption may induce a series of diseases, including osteoarthritis, osteoporosis and aseptic peri-implant loosening. . Ovary Insufficiency. In the double-blind phase, half of the participants will receive nirogacestat while the other half will receive placebo. 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). Primary ovarian insufficiency may be caused by: Chromosome changes. Gynecologic anomalies, including uterine agenesis and ovarian dysgenesis, are some of the several differential diagnoses in adolescent females with primary amenorrhea and delayed puberty. nirogacestat. Many women naturally experience reduced fertility when they are about 40 years old. - Participant has an abnormal QT interval at screening. The usual age for egg production to stop, known as menopause, is around 50. 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. Nirogacestat (PF-03084014) is a potent, small molecule, selective, reversible, noncompetitive inhibitor of -secretase (GS) with a potential antitumor activity. However, this terminology has fallen out of favor as the degree . Bone Loss and Fracture Risk. The FDA has granted a breakthrough therapy designation to the investigational gamma-secretase inhibitor nirogacestat (PF-03084014) for the treatment of adult . Background. . Ovarian insufficiency occurs in approximately 1% of women. Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors. Share this article. This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). When adolescents present with primary amenorrhea and no associated comorbidities, 50% are found to have abnormal karyotypes. September 29, 2022, 10:30 AM UTC. Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation. Some genetic disorders are associated with primary ovarian insufficiency. This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). 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 . In the double-blind phase, half of the .. . Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which may contribute to desmoid tumor growth. In women with this condition, the ovaries (organs that produce a woman's eggs) stop producing eggs before age 40. Monoisotopic mass 489.327911 Da. Women with POI present in primary care with menstrual . Premature ovarian insufficiency (POI) occurs in women aged under 40 years and is a syndrome consisting of amenorrhoea, elevated gonadotrophins and oestrogen deficiency. Nirogacestat was generally well tolerated with a manageable safety profile. SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe 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. 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 . Background:-Desmoid tumors (also known as aggressive fibromatosis), are rare, locally invasive, slow-growing soft-tissue tumors. 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. Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation. Final gross price and currency may vary according to local VAT and billing address. 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]. 1 The breakthrough designation was granted as a result of positive findings seen in phase I and II trials of nirogacestat monotherapy . Gamma-secretase, a proteolytic enzyme complex, mediates processing of several integral membrane proteins including amyloid precursor protein and Notch. 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. Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. Typical symptoms found when the menopause occurs later, such as hot flushes and night sweats, may not be present. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. ICH GCP. View Full Description Full Description Nirogacestat (PF-03084014) Investigational Device(s) None . Primary ovarian insufficiency is suspected in women < 40 with unexplained infertility, menstrual abnormalities, or symptoms of estrogen deficiency. Nirogacestat has been used in trials studying the treatment of Breast Cancer, HIV Infection, . This disease spectrum has previously been referred to as premature ovarian failure. 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 selective gamma secretase inhibitor [1] developed by SpringWorks Therapeutics that has potential anti-tumor activity. [2] MedKoo CAT#: 525757. The disease can be either asymptomatic or be associated with severe loss of . Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors. Among important research news last week, US pharma giant Merck & Co released positive Phase III results for the pulmonary arterial . The study will enroll approximately 40 patients who will receive 150mg of nirogacestat twice daily. 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 . Eligibility Requirements: Reduce drug development failure rates. Among younger women (aged 30 years or younger) with secondary amenorrhea, 13% also have been noted . September 4, 2019. Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective -secretase inhibitor with an IC50 of 6.2 nM. symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. 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. Trial Description: This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). 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. 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 . Primary ovarian insufficiency: an overview. Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.. Clinical Trials Registry. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers. Primary ovarian insufficiency (POI), also known as premature ovarian failure, happens when a woman's ovaries stop working normally before she is 40. 4 Nirogacestat elicited an ORR of 29.4%, with no progressive. 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