Very common side effects in the first day or two may include: having a painful, heavy feeling and tenderness in the arm where you. feeling tired. Nirogacestat | C27H41F2N5O | CID 46224413 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities . The effects of nirogacestat have been evaluated in experimental models. Nirogacestat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. nirogacestat (100 mg BID continuously) combination in patients with heavily pretreated RRMM. SpringWorks is in the process of testing Nirogacestat as a monotherapy in patients with desmoid tumors. Nirogacestat was shown to be safe with manageable side effects; 95% of treatment-emergent adverse events were low grade. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed. When compared to potential competing drugs sorafenib and AL102, nirogacestat is the best, Nierengarten noted. Support for Caregivers. Pain at the injection site was also the most common complaint among people boosted with Pfizer's updated vaccine; about 60 percent of trial participants reported it. Again, the median PFS had not yet been reached at the time of the publication data because of a lack of tumor progression events. Clinical Trials Information. In the double-blind phase, half of the participants will receive nirogacestat while the other half will receive placebo. If these problems occur, they usually begin soon after vaccination and are mild and short-lived. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers. Nirogacestat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Treatment with nirogacestat resulted in a 71% reduction in the risk of disease progression among adults with progressing desmoid tumors. Feelings and Cancer. Its therapeutic effects currently are being investigated in heavily treated patients with multiple myeloma that has relapsed or failed to respond to treatment (refractory). Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). "Desmoid tumors are aggressive soft-tissue tumors that can lead to severe negative outcomes for patients, including long-lasting pain, disfigurement, and amputation. Monoisotopic mass 489.327911 Da. We report four cases of pediatric and young adult desmoid tumor patients (three with familial adenomatous polyposis [FAP] syndrome) who received nirogacestat on compassionate use. As with any medicine, there is a very remote chance of a vaccine causing a severe allergic reaction, other serious injury, or death. These common side effects are much less . Patients should recover from the serious side effects of previous therapies before receiving nirogacestat. Echemi supplies various nirogacestat side effects news. Side effects generally go away in a few days. Self-Image & Sexuality. In the double-blind phase, half of the participants will receive nirogacestat while the other half will receive placebo. This phase II trial studies the side effects and how well nirogacestat works in treating patients patients less than 18 years of age with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. 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 . Published: May 26, 2022, 9:15 PM UTC GlobeNewswire - Initial Data to be Presented from GSK-Sponsored Phase 1/2 Study Evaluating Nirogacestat in Combination with Low-Dose BLENREP in Patients with Relapsed or Refractory Multiple Myeloma - PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. Nirogacestat enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Molecular Formula CHFNO. No dose reductions occurred in the placebo arm, and only one discontinuation was reported. Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft . fever (temperature 37.8C or above) feeling generally unwell. Nirogacestat is an investigational, oral, selective, small molecule gamma-secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and. Nirogacestat is an investigational, oral, small molecule, selective gamma-secretase inhibitor. This phase II trial studies the side effects and how well nirogacestat works in treating patients patients less than 18 years of age with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. It is easy to find the trends and top topics of nirogacestat side effects here. in preclinical models, nirogacestat has been shown to increase the cell surface density of bcma and reduce levels of soluble bcma, which may enhance the activity of bcma-targeted therapies. This ongoing sub-study is actively recruiting patients and will continue to evaluate belamaf + nirogacestat efficacy and safety. The analyst recapped the DeFi study results. Prune juice may help make bowel movements softer. Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. Day-to-Day Life. Nirogacestat enhances docetaxel-mediated tumor response and provides a rationale to explore GSIs as adjunct . . Via this mechanism, nirogacestat may enhance the activity of BCMA-targeted therapies. Very common side effects in the first day or two include: having a painful, heavy feeling and tenderness in the arm where you had your injection. Research. Others have side effects that affect their ability to do daily activities. Requests cannot be made directly by an individual patient or a patient's parent/legal guardian or caregiver. Bloating or swelling of the face, arms, hands, lower legs, or feet burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings difficult or labored breathing feeling faint, dizzy, or lightheadedness feeling of warmth or heat flushing or redness of the skin, especially on the face and neck headache rapid weight gain 8019 Background: Preclinical data demonstrate that nirogacestat, a gamma-secretase inhibitor, may increase cell-surface levels of a B-cell maturation antigen (BCMA) and reduce soluble BCMA levels, which could enhance anti-BCMA agent activity in multiple myeloma. diarrhoea, nausea and vomiting. This phase II trial studies the side effects and how well nirogacestat works in treating patients patients less than 18 years of age with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. Purpose. PF-03084014 does not show a paradoxical increase in plasma A at low concentrations in both preclinical species and humans. Nirogacestat (PF-03084014) is a potent, small molecule, selective, reversible, noncompetitive inhibitor of -secretase (GS) with a potential antitumor activity. Nirogacestat may stop the growth of tumor cells by blocking some of the . Can be aggressive or slow-growing. headache, aches and chills. Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft . A new drug application for nirogacestat is expected to be submitted to the FDA in the second half of 2022. Requests for access to a SpringWorks investigational therapy must be made voluntarily by the patient's treating physician. Mary Smith, PhD, senior vice president of clinical research and development at SpringWorks Therapeutics explains the how nirogacestat works to treat individu. An online community for patients and their families Nirogacestat DeFi Trial Side Effects This conversation is about NCT03785964 Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) [phase 3] desmoid tumor Non-metastasizing tumors that can develop almost anywhere in the body. "In terms of efficacy, we view nirogacestat as numerically better than both sorafenib and AL102," Nierengarten wrote. At the time of submission of the application for orphan designation, clinical trials with nirogacestat in patients with soft tissue sarcoma were ongoing. This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). Nirogacestat: Type: Formula: C 27 H 41 F 2 N 5 O: Weight: Average: 489.656 Monoisotopic: 489.327917286 : Groups: Investigational: Therapeutic Class: Manufacturer: Available Country: Last Updated: August 5, 2021 at 12:40 pm: Structure Nirogacestat Structure. Description: Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. Nirogacestat DrugBank Accession Number DB12005 Background Nirogacestat has been used in trials studying the treatment of Breast Cancer, HIV Infection, Desmoid Tumors, Advanced Solid Tumors, and Aggressive Fibromatosis, among others. Nirogacestat enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Nirogacestat may stop the growth of tumor cells by blocking some of the enzymes . headache, aches and chills. The primary endpoint, improvement in progression-free survival compared to placebo (p<0.001), was achieved, with patients in all . Nirogacestat (gamma secretase inhibitor) Gamma secretase cleaves multiple transmembrane proteins, including Notch, that are believed to play a role in activating pathways that contribute to growth of desmoid and ovarian granulosa cell tumors. Nirogacestat ( PF-03084014) is a selective gamma secretase inhibitor [1] developed by SpringWorks Therapeutics that has potential anti-tumor activity. Nirogacestat is being investigated for the treatment of desmoid tumors due to its ability to bind to GS, blocking proteolytic activation of Notch receptors. 1 in. mild flu-like symptoms. Summary. This is being tested in a phase 3 study known as DeFi. dizziness, lightheadedness, nausea, and. The most common grade 3 or greater TEAEs in the nirogacestat and placebo arms, respectively, included diarrhea (16% vs 1%), maculopapular rash (6% vs 0%), stomatitis (4% vs 0%), fatigue (3% vs. nirogacestat. Nirogacestat is a selective gamma secretase (GS) inhibitor with potential antitumor activity. Side effects after getting a COVID-19 vaccine can vary from person to person. At the time of submission, nirogacestat was not authorised anywhere in the EU for the treatment of soft tissue sarcoma. In the DREAMM-5 (NCT04126200) Phase I/II platform trial belantamab mafodotin (belamaf; BLENREP), a BCMA-targeting antibody-drug . Eat foods high in fiber to make it easier to have a bowel movement. 29 Sep 2022 SpringWorks Therapeutics plans to submit NDA for fibroma to the US FDA in the second half of 2022. Nirogacestat, also known as PF-03084014, is a potent and selective gamma secretase (GS) inhibitor with potential antitumor activity. ChemSpider ID 26232306. For more information about this study and to inquire about eligibility, please contact 1- 833-MSK-KIDS . flushing (warmth, redness, or tingly feeling under your skin). [2] In the double-blind phase, half of the participants will receive nirogacestat while the other half will receive placebo. Conclusions -nirogacestat gamma secretase inhibitor Exciting potential for use in desmoid patients 72% RECIST response rate Active at even low doses (as low as 80mg BID) Tolerable side effect profile (primarily diarrhea, hypophosphatemia) Clinical benefit in 100% of patients (only patient with progression had This phase II trial studies the side effects and how well nirogacestat works in treating patients with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. This study is for patients over 1 year of age and under age 18. Adjusting to Cancer. Other typical side effects included fatigue, headache, muscle pain, chills, joint pain, diarrhea, fever and vomiting all were seen with Pfizer's original COVID-19 booster too. Nirogacestat exhibited a manageable safety profile in the DeFi trial, with 95% of all treatment-emergent adverse events (TEAEs) reported as Grade 1 or 2. PF-03084014 in combination with dexamethasone elicits antileukemic effects in T-cell acute lymphoblastic leukemias (T-ALL). Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective -secretase inhibitor with an IC50 of 6.2 nM. We report four cases of pediatric and young adult desmoid tumor patients (three with familial adenomatous polyposis [FAP] syndrome) who received nirogacestat on compassionate use. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. Type Small Molecule Groups Investigational Structure 3D Download Similar Structures Weight Average: 489.656 The median dose intensity was 288.3 mg/d (range, 169-300) with nirogacestat and 300.0 mg/d with placebo (range, 239-300). Dose reductions were common in the nirogacestat arm at 42% (n = 29), but few patients required discontinuation (n = 14; 20%). Good examples are high-fiber cereals, beans, vegetables, and whole-grain breads. Nirogacestat binds to GS, blocking proteolytic activation of Notch receptors; Notch signaling pathway inhibition may follow, which may result in the induction of apoptosis in tumor cells that overexpress Notch. Nirogacestat is an investigational, oral, selective, small molecule gamma-secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. 1 Emerging clinical data also suggest that a GSI may increase antitumor efficacy of BCMA-targeted autologous CAR T therapy in patients with relapsed or refractory multiple myeloma. Side Effects of Cancer Treatment. flushing as your body adjusts to this medication. Side effects of the coronavirus (COVID-19) vaccination. It was granted FDA breakthrough drug designation in September 2019 for adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. Once participants are eligible to roll into the open-label phase, they will receive nirogacestat.. Clinical Trials Registry. Heat can cause a syncope episode. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. Once participants are eligible to roll into the open-label phase, they will receive nirogacestat. B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with multiple myeloma. Appetite loss Frequent or recurrent infections Unintended weight loss Bone pain which may be worse in the spine or chest Nausea Fatigue Bone fractures Weakness or numbness in the legs Excessive thirst and frequent urination Constipation Mental confusion Hypercalcemia (excess calcium levels) What are your thoughts on being a rare disease advocate? Limit activity done outside on hot days. PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors. Median progression-free survival (PFS), in nirogacestat arm and placebo arm, were found to be, not estimable and 15.1 months, respectively at a median follow-up of 19.2 months (HR, 0.29; P < 0.001) Patient-reported outcomes ( PROs ), nirogacestat led to a significant reduction in pain severity at cycle 10 of treatment compared with placebo (P<0 . In agreement, preclinical data showed that myeloma cell death increased by 3,000 times when nirogacestat was added to GlaxoSmithKline 's Blenrep. Nirogacestat is an oral, small molecule that works by blocking gamma secretase , an enzyme that cleaves and detaches BCMA from the surface of myeloma cells. Average mass 489.644 Da. The most frequently reported TEAEs in participants receiving nirogacestat as compared to the placebo arm were diarrhea (84% vs 35%), nausea (54% vs 39%), and fatigue (51% vs 36%). By blocking gamma secretase, nirogacestat is expected to increase the amount of BCMA on the surface of cancer cells, and boost the effectiveness of BCMA-targeted therapies. Results Encouraging clinical activity and a manageable safety profile is observed with low dose belamaf (0.95 mg/kg Q3W) + nirogacestat (100 mg twice daily, continuously) in patients with RRMM. This phase II trial studies the side effects and how well nirogacestat works in treating patients patients less than 18 years of age with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment. SpringWorks Therapeutics Highlights Nirogacestat Clinical Data at the 2022 ASCO Annual Meeting. However, whether it has the therapeutic effect on abnormal bone resorption remains to be evaluated. This is a randomized double-blind . Reduced ocular events, particularly Grade 3, 12.5% (2/10 in DE and 1/14 in CE) were observed in patients dosed with low dose belamaf + nirogacestat. Other side effects of Nitrostat include: mild burning or tingling with the tablet in your mouth, and.
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