DOCSLIB.ORG

Brain Tumors

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Brain Tumors Brain Tumors Ependymoma treatment protocols Study Clinical trial name Phase/type Age AflacST1502: A Phase II Study of Sirolimus in AflacST1502 Combination with Metronomic Chemo-therapy in Children II >12 mo to <30 yr CHOANOME II with Recurrent and/or Refractory Solid and CNS Tumors https://clinicaltrials.gov/ct2/show/NCT02574728 ADVL1823, Larotrectinib (LOXO-101, NSC# 788607, IND# 141824) for Previously Untreated TRK Fusion COG Pediatric Solid Tumors and TRK Fusion Relapsed II <30 yr ADVL1823 Pediatric Acute Leukemias https://clinicaltrials.gov/ct2/show/NCT03834961 APEC1621A: NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of COG >12 mo to LOXO-101 (Larotrectinib) in Patients with Tumors II APEC1621AREQ <21 yr Harboring Actionable NTRK Fusions https://clinicaltrials.gov/ct2/show/NCT03213704 APEC1621B: NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of COG JNJ-42756493 (Erdafitinib) in Patients with Relapsed >12 mo to II APEC1621BREQ Pediatric Solid Tumors Harboring FGFR1/2/3/4 <21 yr Alterations https://clinicaltrials.gov/ct2/show/NCT03210714 APEC1621C: NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice) - Phase 2 Subprotocol of >12 mo to II APEC1621CREQ Tazemetostat in Patients with Tumors Harboring <21 yr Alterations in EZH2 or Members of the SWI/SNF Complex https://clinicaltrials.gov/ct2/show/NCT03213665 APEC1621D NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice) – Phase 2 Subprotocol of II >12 mo to <21 yr APEC1621DREQ LY3023414 in Patients with Solid Tumors https://clinicaltrials.gov/ct2/show/NCT03213678 APEC1621E NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) – Phase 2 Subprotocol of COG Selumetinib in Patients with Tumors Harboring Activating II >12 mo to <21 yr APEC1621EREQ MAPK Pathway Mutations https://clinicaltrials.gov/ct2/show/NCT03213691 APEC1621F NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice) – Phase 2 Subprotocol of II >12 mo to <21 yr APEC1621FREQ Ensartinib in Patients with Tumors Harboring ALK or ROS1 Genomic Alterations https://clinicaltrials.gov/ct2/show/NCT03213652 Page 1 of 20 February 28, 2020 CNS APEC1621G NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) – Phase 2 Subprotocol of COG Vemurafenib in Patients with Tumors Harboring II >12 mo to <21 yr APEC1621GREQ Actionable BRAF V600 Mutations https://clinicaltrials.gov/ct2/show/NCT03220035 APEC1621H NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice)—Phase 2 Subprotocol of II >12 mo to <21 yr APEC1621HREQ Olaparib in Patients with Tumors Harboring Defects in DNA Damage Repair Genes https://clinicaltrials.gov/ct2/show/NCT03233204 APEC1621I NCI-COG Pediatric MATCH (Molecular Analysis COG for Therapy Choice)—Phase 2 Subprotocol of Palbociclib in APEC1621IREQ Patients with Tumors Harboring Activating Alterations in Cell II >12 mo to <21 yr Cycle Genes https://clinicaltrials.gov/ct2/show/NCT03526250 APEC1621J NCI-COG Pediatric MATCH (Molecular Analysis COG for Therapy Choice)—Phase 2 Subprotocol of BVD-523FB APEC1621JREQ (Ulixertinib) in Patients with Tumors Harboring Activating II >12 mo to <21 yr MAPK Pathway Mutations https://clinicaltrials.gov/ct2/show/NCT03698994 A Phase 1/1b, Open-Label, Dose-Escalation and Expansion Ignyta Study of Entrectinib (RXDX-101) in Children and Adolescents >2 to RXDX-101-03 with Recurrent or Refractory Solid Tumors and Primary CNS I/Ib <22 yr Tumors https://clinicaltrials.gov/ct2/show/NCT02650401 LOXO-EXT-17005: A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects with Previously LOXO-EXT-17005 I/II >1 mo Treated NTRK Fusion Cancers https://clinicaltrials.gov/ct2/show/NCT03215511 Aflac ST1501, A Phase I Study of Abemaciclib in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma and in ≥2 to AflacST1501 Children with Recurrent and Refractory Solid Tumors I <25 yr Including Malignant Brain Tumors https://clinicaltrials.gov/ct2/show/NCT02644460 Aflac ST1601: A Phase I Trial of Temozolomide and >3 to AflacST1601 Everolimus in Children with Recurrent or Refractory Brain I <22 yr Tumors PBTC-045: A Safety and Preliminary Efficacy trial of MK- 3475 (pembrolizumab; anti-PD-1) in Children with Recurrent, Progressive or Refractory Diffuse Intrinsic Pontine Glioma >1 to PBTC-045 (DIPG), I <18 yr Non-brainstem High-grade Gliomas (NB-HGG), Ependymoma, Medulloblastoma and Hypermutated Brain Tumors https://clinicaltrials.gov/ct2/show/NCT02359565 PBTC-048: Feasibility Trial of Optune for Children with >5 to PBTC-048 Recurrent or Progressive Supratentorial High-grade Glioma I <21 yr and Ependymoma Page 2 of 20 February 28, 2020 CNS PBTC-050: A Phase I and Surgical Study of Ribociclib and Everolimus (RAD001) in Children with Recurrent or >1 to I PBTC-050 Refractory Malignant Brain Tumors <21 yr https://clinicaltrials.gov/ct2/show/NCT03387020 Phase I Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Pediatric >1 to I PBTC-051 Subjects with Recurrent/ Refractory Brain Tumors and Newly <21 yr Diagnosed Brain Stem Glioma https://clinicaltrials.gov/ct2/show/NCT03389802 ADVL1615, A Phase 1 Study of Pevonedistat (MLN4924 Part A1: >12 mo to <21 yr COG IND# 136078), a NEDD8 Activating Enzyme (NAE) Inhibitor, I Part A2: ADVL1615 in Combination with Temozolomide and Irinotecan in >6 mo to <12 mo Pediatric Patients with Recurrent or Refractory Solid Tumors https://clinicaltrials.gov/ct2/show/NCT03323034 Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Palbociclib (Ibrance®) in Combination with Irinotecan and COG >2 to Temozolomide in Pediatric Patients with Recurrent or I ADVL1921 <21 yr Refractory Solid Tumors https://clinicaltrials.gov/ct2/show/NCT03709680 Ependymoma supportive treatment and non-therapeutic protocols Non- AflacPM1702 Aflac Precision Medicine Program (APMP) Study <30 yr therapeutic COG APEC14B1: The Project:Everychild Protocol: Non- APEC14B1 A Registry, Eligibility Screening, Biology and Outcome Study <25 yr therapeutic https://clinicaltrials.gov/ct2/show/NCT02402244 APEC1621SC: NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice) Screening Protocol NA >12 mo to <21 yr APEC1621SC https://clinicaltrials.gov/ct2/show/NCT03155620 Key Adverse Events after Childhood Cancer (cardiac, stroke, COG Non- secondary malig)/closed to AVN patients as of 11-26-08 <21 yr at dx ALTE03N1 therapeutic https://clinicaltrials.gov/ct2/show/NCT00082745 COG Umbrella Long-Term Follow-Up Protocol Non- All ages ALTE05N1 https://clinicaltrials.gov/ct2/show/NCT00736749 therapeutic Health-related Quality of Life Outcomes during Molecularly QOL Targeted Tx Non- Targeted Therapy for the Treatment of High Risk Pediatric <21 yr Brain Tumors therapeutic Brain Tumors Germ cell tumor treatment protocols ADVL1823, Larotrectinib (LOXO-101, NSC# 788607, IND# 141824) for Previously Untreated TRK Fusion Pediatric Solid COG Tumors and TRK Fusion Relapsed Pediatric Acute II <30 yr ADVL1823 Leukemias https://clinicaltrials.gov/ct2/show/NCT03834961 Page 3 of 20 February 28, 2020 CNS APEC1621A: NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of COG >12 mo to LOXO-101 (Larotrectinib) in Patients with Tumors Harboring II APEC1621AREQ <21 yr Actionable NTRK Fusions https://clinicaltrials.gov/ct2/show/NCT03213704 APEC1621B: NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of JNJ- COG >12 mo to 42756493 (Erdafitinib) in Patients with Relapsed Pediatric II APEC1621BREQ <21 yr Solid Tumors Harboring FGFR1/2/3/4 Alterations https://clinicaltrials.gov/ct2/show/NCT03210714 APEC1621C: NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice) - Phase 2 Subprotocol of >12 mo to II APEC1621CREQ Tazemetostat in Patients with Tumors Harboring Alterations <21 yr in EZH2 or Members of the SWI/SNF Complex https://clinicaltrials.gov/ct2/show/NCT03213665 APEC1621D NCI-COG Pediatric MATCH (Molecular COG Analysis for Therapy Choice) – Phase 2 Subprotocol of II >12 mo to <21 yr APEC1621DREQ LY3023414 in Patients with Solid Tumors https://clinicaltrials.gov/ct2/show/NCT03213678 APEC1621E NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) – Phase 2 Subprotocol of Selumetinib in COG Patients with Tumors Harboring Activating MAPK Pathway II >12 mo to <21 yr APEC1621EREQ Mutations https://clinicaltrials.gov/ct2/show/NCT03213691 APEC1621F NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) – Phase 2 Subprotocol of Ensartinib in COG Patients with Tumors Harboring ALK or ROS1 Genomic II >12 mo to <21 yr APEC1621FREQ Alterations https://clinicaltrials.gov/ct2/show/NCT03213652 APEC1621G NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) – Phase 2 Subprotocol of COG Vemurafenib in Patients with Tumors Harboring Actionable II >12 mo to <21 yr APEC1621GREQ BRAF V600 https://clinicaltrials.gov/ct2/show/NCT03220035 APEC1621H NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)—Phase 2 Subprotocol of COG Olaparib in Patients with Tumors Harboring Defects in DNA II >12 mo to <21 yr APEC1621HREQ Damage Repair Genes https://clinicaltrials.gov/ct2/show/NCT03233204 APEC1621I NCI-COG Pediatric MATCH (Molecular Analysis COG for Therapy Choice)—Phase 2 Subprotocol of Palbociclib in II >12 mo to <21 yr APEC1621IREQ Patients with Tumors Harboring Activating Alterations in Cell Cycle Genes https://clinicaltrials.gov/ct2/show/NCT03526250 APEC1621J NCI-COG Pediatric MATCH (Molecular Analysis COG for Therapy Choice)—Phase
Load more

Recommended publications
  • Systematic Review: Targeting HER2 in Bladder Cancer
    Bladder Cancer 5 (2019) 1–12 1 DOI 10.3233/BLC-180196 IOS Press Systematic Review Systematic Review: Targeting HER2 in Bladder Cancer Vadim S. Koshkina, Peter O’Donnellb,EvanY.Yuc and Petros Grivasd,∗ aDepartment of Medicine, Division of Hematology and Oncology, University of California San Francisco, CA, USA bDepartment of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA cDepartment of Medicine, Division of Oncology, Clinical Research Director, Fred Hutchinson Cancer Research Center, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA dDepartment of Medicine, Division of Oncology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA Received 23 August 2018 Accepted 22 November 2018 Abstract. Background: HER2 (ErbB2) is a receptor of the Human Epidermal Growth Factor Receptor (HER) family whose role in oncogenesis of numerous malignancies is well described. Drugs targeting HER2 are currently approved in breast and gastroesophageal cancers while pan-HER targeting agents are being evaluated in multiple malignancies. HER2 genomic alterations are commonly described in urothelial cancer and multiple trials have assessed the efficacy of anti-HER2 agents in both muscle-invasive and metastatic urothelial carcinoma. Objective: To review prospective clinical trials of therapeutic agents with HER2–targeting activity in patients with bladder cancer. Methods: A systematic search of PubMed, ASCO abstracts and Clinicaltrials.gov was performed to identify studies of HER2–targeting agents in bladder cancer. Reported results from prospective trials were reviewed and summarized. Results: Eleven prospective clinical trials with reported results were identified that investigated activity of trastuzumab, lapatinib, neratinib, afatinib, or autologous cellular immunotherapy, (DN24–02), in various bladder cancer treatment settings.
    [Show full text]
  • Clinical Development of FGFR3 Inhibitors for the Treatment of Urothelial Cancer
    Bladder Cancer 5 (2019) 87–102 87 DOI 10.3233/BLC-180205 IOS Press Review Clinical Development of FGFR3 Inhibitors for the Treatment of Urothelial Cancer Tony Ibrahima, Marco Gizzib, Ratislav Bahledac and Yohann Loriota,d,∗ aD´epartement de M´edecine Oncologique, Gustave Roussy, Universit´e Paris-Sud, Universit´e Paris-Saclay, Villejuif, France bDepartment of Medical Oncology. Grand Hˆopital de Charleroi, Charleroi, Belgium cDrug Development Department (DITEP), Gustave Roussy, Villejuif France dInserm 981, Universit´e Paris-Sud, Universit´e Paris Saclay, Villejuif, France Received: 29 November 2018 Accepted: 4 March 2019 Abstract. The fibroblast growth factor receptor 3 (FGFR3) plays critical roles in driving oncogenesis of a subset of patients with urothelial carcinomas (UC). Growing evidence from preclinical studies suggests that FGFR3 inhibition can reduce proliferation and survival in vitro and in vivo models of FGFR3-altered UC. Early clinical trials investigating selective FGFR3 inhibitor have reported preliminary signs of antitumor activity in advanced UC patients with selected FGFR3 mutations or fusions. Currently, phase 3 trials with erdafitinib and rogaratinib are enrolling patients with known FGFR3 alterations. Future combinations with targeted therapies or immune checkpoint inhibitors may increase the efficacy of selective FGFR3 inhibitors. Herein, we discuss current clinical development of FGFR3 inhibitors as well as unsolved questions with regards to patient selection, management of toxicities and mechanisms of resistance to selective FGFR3 inhibitors. Keywords: Urothelial cancer, bladder cancer, fibroblast growth factor 3, tyrosine kinase INTRODUCTION the treated patients [1–11]. Innovative strategies aim- ing to improve metastatic UC treatment efficacy have Metastatic urothelial carcinoma (UC) is frequent learned from targeted therapies in solid tumors such and has a poor prognosis.
    [Show full text]
  • New ADC Shrinks HER2-Positive Tumors
    Published OnlineFirst August 2, 2019; DOI: 10.1158/2159-8290.CD-NB2019-089 NEWS IN BRIEF he says, “I can’t cancer, and 17 had HER2-low HR- fathom that cost.” negative breast cancer. The remaining Cytoplasm –Elie Dolgin n 47 patients had gastric, urothelial, or endometrial tumors. Eye-related side effects were again New ADC prevalent: 71% of patients were Shrinks affected by problems such as conjunc- tivitis, keratitis, and dry eye. These Nuclear pore HER2- adverse effects have been seen with complex Positive other ADCs—although they haven’t Tumors been described with T-DM1—but the mechanism remains unclear, says A novel co-author Philippe Aftimos, MD, of Nucleus antibody–drug the Jules Bordet Institute and the Free conjugate (ADC) University of Brussels in Belgium. Tumor suppressor protein Selective inhibitor of triggers responses nuclear export inhibitor The ADC produced partial + eiF4E-bound mRNA in patients with Regulatory factor XPO1 responses in 33% of the patients with HER2-expressing HER2-positive metastatic breast breast cancer Selinexor is a selective inhibitor of nuclear export. By blocking XPO1, it cancer; 28% with HER2-low, HR- prevents molecular cargo from moving through the nuclear pore complex, and other solid positive metastatic breast cancer; and causing cell-cycle arrest, apoptosis, and other antitumor activity. (Courtesy tumors, a phase I 40% with HER2-low, HR-negative of Karyopharm Therapeutics; modified with permission.) clinical trial metastatic breast cancer. The median indicates (Lancet progression-free survival for these Oncol 2019;20:1124–35). The drug commonly experienced side effects three groups was 7.6 months, such as thrombocytopenia, hypona- could become a new treatment for 4.1 months, and 4.9 months, respec- tremia, anemia, and nausea.
    [Show full text]
  • | TIME TRIALS February 2021 Provides You Access to a Network of Just-In-Time Biomarker-Driven Trials for Your Patients
    Your organization has enrolled in the TIME TrialTM Network, which | TIME TRIALS February 2021 provides you access to a network of just-in-time biomarker-driven trials for your patients. Studies currently enrolling in the TIME TrialTM Program: SOLID TUMOR SOLID TUMOR CONT. Elevation ELVAP-001-01 Ideaya IDE196-001 GNAQ/11 hotspot mutation (CRESTONE) Phase I/II At least 1 prior standard therapy; NRG1 fusion Phase II NCT03947385 No prior treatment with a PKC At least 1 prior standard therapy NCT04383210 IDE196 inhibitor Seribantumab Janssen CAN2002 (RAGNAR) FGFR 1-4 fusions & specified Phase II mutations BREAST NCT04083976 At least 1 prior standard therapy JNJ-42756493 (Erdafitinib) Excludes Bladder Cancer HER2-, ER+ & ESR1 mutations Sermonix SMX 18-001 (ELAINE I) Progression following AI in Phase II Turning Point TPX-0005-01 combination with a CDK 4/6 inhibitor; (TRIDENT) NCT03781063 NTRK 1-3 fusions No more than 1 prior systemic Phase II Lasofoxifene or Fulvestrant Allowed up to 2 prior TRK TKIs chemotherapy NCT03093116 TPX-0005 (Repotrectinib) Sermonix SMX 20-001 (ELAINE II) HER2-, ER+ & ESR1 mutations Phase II Progression following first or second- Blueprint BLU-667-101 (ARROW) RET fusion NCT04432454 line hormone therapy; No more than 1 Phase I/II At least 1 prior standard therapy; no Lasofoxifene & Abemaciclib prior systemic chemotherapy NCT03037385 prior treatment with a selective RET Pralsetinib (BLU-667) inhibitor ; Excludes MTC and NSCLC Ayala AL-TNBC-01 (TENACITY) Notch Activation Phase II No more than three lines of systemic Merus
    [Show full text]
  • Agents Available Under CTEP Collaborative Agreements for Clinical and Non-Clinical Studies 1 As of 7/28/2021
    Agents Available Under CTEP Collaborative Agreements for Clinical and Non-clinical Studies 1 as of 7/28/2021 Pharmaceutical Agent Name Alternate Name Collaborator NSC Number Drug Monitor Mechanism of Action Targets Classes abemaciclib LY2835219 Eli Lilly 783671 Piekarz CDK4/6 inhibitor CDK4/6 Small Molecule AMG510 Amgen 825510 Wright Inhibits G12C-mutated KRAS mutated KRAS protein Small Molecule Anti cell surface glycoprotein mesothelin conjugated to anetumab maytansinoid DM4 with potential antineoplastic Antibody-Drug Conjugate; ravtansine* BAY 94-9343 Bayer 791065 Moscow activity mesothelin Monoclonal Antibody anti-apoptotic Bcl-2 family Inhibits B-cell lymphoma 2 (Bcl-2) and B-cell proteins, including Bcl-2, Bcl-xL, APG-1252*** Pelcitoclax Ascentage 831685 Gore lymphoma – extra-large (Bcl-xL) Bcl-w, and Mcl-1 Small Molecule Combination of cedazuridine and ASTX727 decitabine Astex Pharmaceuticals 820631 Piekarz DNA methyltransferase (DNMT) inhibitor DNA methyltransferase Small Molecule Targets PD-L1 expressed on tumor and infiltrating programmed cell death ligand 1 Atezolizumab MPDL3280A Genentech 783608 Sharon immune cells, preventing binding to PD-1 and B7.1 (PD-L1) Monoclonal Antibody AZD5363 Capivasertib AstraZeneca 782347 Sandlund Inhibits all AKT isoforms AKT Small Molecule Inhibits Ataxia Telangiectasia and Rad3 related (ATR) AZD6738 AstraZeneca 802785 Gore serine/threonine protein kinase ATR Small Molecule Inhibitor of ataxia telangiectasia mutated and Rad3- BAY1895344 Bayer 810486 Gore related (ATR) kinase ATR Small Molecule
    [Show full text]
  • (Erdafitinib), a Functionally Selective Small Molecule FGFR Family Inhibitor
    Author Manuscript Published OnlineFirst on March 24, 2017; DOI: 10.1158/1535-7163.MCT-16-0589 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Discovery and pharmacological characterization of JNJ-42756493 (erdafitinib), a functionally selective small molecule FGFR family inhibitor Timothy P.S. Perera1, Eleonora Jovcheva1, Laurence Mevellec2, Jorge Vialard1, Desiree De Lange1, Tinne Verhulst1, Caroline Paulussen1, Kelly Van De Ven1, Peter King1, Eddy Freyne1, David C. Rees3, Matthew Squires3, Gordon Saxty3, Martin Page1, Christopher W. Murray3, Ron Gilissen1, George Ward3, Neil T. Thompson3, David R. Newell4, Na Cheng5, Liang Xie5, Jennifer Yang5, Suso J. Platero6, Jayaprakash D. Karkera6, Christopher Moy6, Patrick Angibaud2, Sylvie Laquerre6 and Matthew V. Lorenzi6,7. 1Janssen Research and Development, Beerse, Belgium. 2Janssen Research and Development, Val de Reuil, France. 3Astex Pharmaceuticals, Cambridge, United Kingdom. 4Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK. 5Janssen Research and Development, Shanghai, China. 6Janssen Research and Development, Spring House, USA. 7To whom correspondence should be addressed: Matthew V. Lorenzi, Oncology Discovery, Janssen R&D, 1400 McKean Road, Spring House, PA 19477. Phone: 215 793-7356; E-mail: [email protected] Disclosure of Potential Conflicts of Interest: T.P.S. Perera, E. Jovcheva, L. Mevellec, J. Vialard, D. De Lange, T. Verhulst, C. Paulussen, K. Van De Ven, P. King, E. Freyne, M. Page, R. Gilissen, N. Cheng, L. Xie, J. Yang, S.J. Platero, J.D. Karkera, C. Moy, P. Angibaud, S. Laquerre and M.V. Lorenzi are or have been employees of Janssen R&D, and D.C.
    [Show full text]
  • (Fgfrs): Structures and Small Molecule Inhibitors
    cells Review Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors Shuyan Dai 1, Zhan Zhou 1, Zhuchu Chen 1, Guangyu Xu 2,* and Yongheng Chen 1,* 1 NHC Key Laboratory of Cancer Proteomics & Laboratory of Structural Biology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; [email protected] (S.D.); [email protected] (Z.Z.); [email protected] (Z.C.) 2 Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, Hunan, China * Correspondence: [email protected] (G.X.); [email protected] (Y.C.); Tel.: +731-88872530 (G.X.); +86-731-84327542 (Y.C.) Received: 15 May 2019; Accepted: 12 June 2019; Published: 18 June 2019 Abstract: Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases expressed on the cell membrane that play crucial roles in both developmental and adult cells. Dysregulation of FGFRs has been implicated in a wide variety of cancers, such as urothelial carcinoma, hepatocellular carcinoma, ovarian cancer and lung adenocarcinoma. Due to their functional importance, FGFRs have been considered as promising drug targets for the therapy of various cancers. Multiple small molecule inhibitors targeting this family of kinases have been developed, and some of them are in clinical trials. Furthermore, the pan-FGFR inhibitor erdafitinib (JNJ-42756493) has recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic or unresectable urothelial carcinoma (mUC). This review summarizes the structure of FGFR, especially its kinase domain, and the development of small molecule FGFR inhibitors.
    [Show full text]
  • New Drug Update
    Disclosures I have nothing to disclose. New Drug Update JORDAN BASKETT, PHARMD, BCOP CLINICAL ONCOLOGY PHARMACIST DUKE UNIVERSITY HOSPITAL Recently Approved Agents for Leukemia & Lymphoma Objectives Duvelisib September 2018 CLL/SLL, FL Calaspargase pegol-mknl December 2018 ALL 1. Review pharmacology of newly approved oncology Blastic plasmacytoid agents Tagraxofusp-erzs December 2018 dendritic cell neoplasm 2. Discuss literature supporting approval of the agents Ivosidenib July 2018 AML, IDH1+ 3. Identify clinical pearls for new agents Gilteritinib November 2018 AML, FLT3+ 4. Evaluate place in therapy for newly approved agents Glasdegib November2018 AML Moxetumomab September 2018 Hairy cell leukemia pasudotox-tdfk Mycosis fungoides or Mogamulizumab-kpkc August 2018 Sézary syndrome Duvelisib (Copiktra®) Compared to Idelalisib Approved Duvelisib Idelalisib • September 2018 PI3K-δ and PI3K-γ inhibitor PI3K-δ inhibitor MOA • Inhibits PI3K-δ and PI3K-γ in normal and malignant B-cells Monotherapy In combination with rituximab for CLL/SLL Indication BBW: BBW: • Infection • Hepatotoxicity • Relapsed/refractory CLL/SLL and FL after ≥ 2 prior systemic therapies • Diarrhea, colitis (18%) • Diarrhea, colitis (14%) Dosing & Administration • Cutaneous reactions • Intestinal perforation • Pneumonitis (5%) • Pneumonitis (4%) • 25 mg PO BID Administer Pneumocystis jirovecii (PJP) prophylaxis during treatment and until absolute CD4+ T cell count is > 200 cells/uL Consider antiviral prophylaxis for cytomegalovirus reactivation Copiktra (duvelisib) [package insert]. Needham, MA: Verastem, Inc; 2018. Flinn IW, et al. Blood 2018;132(23):2446-2455. Furman RR, et al. N Engl J Med 2014;370(11):997-1007. 1 Calaspargase pegol-mknl Audience Response #1 (AsparlasTM) How does the mechanism of action for duvelisib differ from idelalisib? Approved A.
    [Show full text]
  • Tyrosine Kinase Inhibitors for Solid Tumors in the Past 20 Years (2001–2020) Liling Huang†, Shiyu Jiang† and Yuankai Shi*
    Huang et al. J Hematol Oncol (2020) 13:143 https://doi.org/10.1186/s13045-020-00977-0 REVIEW Open Access Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001–2020) Liling Huang†, Shiyu Jiang† and Yuankai Shi* Abstract Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient’s genetic alteration features. TKIs have dramatically improved patients’ survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies. Keywords: Tyrosine kinase inhibitors, Solid tumors, Targeted therapy Introduction activation of tyrosine kinases due to mutations, translo- According to GLOBOCAN 2018, an estimated 18.1 cations, or amplifcations is implicated in tumorigenesis, million new cancer cases and 9.6 million cancer deaths progression, invasion, and metastasis of malignancies. occurred in 2018 worldwide [1]. Targeted agents are In addition, wild-type tyrosine kinases can also func- superior to traditional chemotherapeutic ones in selec- tion as critical nodes for pathway activation in cancer.
    [Show full text]
  • New Targets in Endocrine-Resistant Hormone Receptor–Positive Breast Cancer
    New Targets in Endocrine-Resistant Hormone Receptor–Positive Breast Cancer Laura C. Kennedy, MD, PhD, and Ingrid A. Mayer, MD, MSCI Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee Corresponding author: Abstract: Endocrine-based treatments are the backbone of initial Ingrid Mayer, MD therapy for advanced hormone receptor–positive breast cancers. Professor of Medicine Developing new therapeutic strategies to address resistance to Vanderbilt University Medical Center/ endocrine therapy is an area of active research. In this review, we Vanderbilt-Ingram Cancer Center 2220 Pierce Ave 777 PRB discuss targeted therapies that are currently the standard of care, Nashville, TN 37232 as well as agents that are at present under investigation as potential Tel: (615) 936-2033 treatments for advanced hormone receptor–positive breast cancer. Email: [email protected] Introduction Hormone receptor–positive (HR+) breast cancers are the most com- monly identified subtype of breast cancer, accounting for about 70% of early and de novo metastatic breast cancer diagnoses.1,2 Estrogen is the main driver of cancer cell proliferation in HR+ breast cancer. Upon binding with estrogen, the estrogen receptor (ER) acts as both a direct transcription factor and a regulator of other transcription factors to drive cell proliferation.3 Therefore, a key component in the initial treatment of metastatic HR+ breast cancer is estrogen depriva- tion. In the treatment-naive state, most advanced HR+ breast cancers are sensitive to estrogen blockade with either an aromatase inhibitor (AI; eg, letrozole, anastrozole, or exemestane) for postmenopausal women or an AI plus ovarian suppression for premenopausal women. Resistance to endocrine therapy is an inevitable development, however, and may be acquired or primary.
    [Show full text]
  • View of This Manuscript
    Liu Biomarker Research (2019) 7:25 https://doi.org/10.1186/s40364-019-0178-7 EDITORIAL Open Access Cancer biomarkers for targeted therapy Delong Liu1,2 Abstract Tumor-associated antigens (TAA) or cancer biomarkers are major targets for cancer therapies. Antibody- based agents targeting the cancer biomarkers include monoclonal antibodies (MoAbs), radiolabeled MoAbs, bispecific T cell engagers, and antibody-drug conjugates. Antibodies targeting CD19, CD20, CD22, CD30, CD33, CD38, CD79B and SLAMF7 are in clinical applications for hematological malignancies. CD123, CLL-1, B cell maturation antigen, and CD138 are targets for cancer immunotherapeutic agents, including the chimeric antigen receptor - engineered T cells. Immune checkpoint inhibitors (ICIs) against PD-1, PD-L1, and CTLA-4 have led to the revolution of cancer immunotherapy. More ICIs targeting IDO, LAG3, TIM-3, TIGIT, SIGLECs, VISTA and CD47 are being explored. Small molecule inhibitors (SMIs) against tyrosine kinase oncoproteins such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, EGFR, ALK, HER2, VEGFR, FGFR, MEK, and MET have fundamentally changed the landscape of cancer therapy. SMIs against BCL-2, IDHs, BRAF, PI3 kinase, mTOR, PARP, and CDKs have become the mainstay in the treatment of a variety of cancer types. To reduce and avoid off-tumor toxicities, cancer-specific TAAs such as CD33 are being manufactured through systems biology approach. Search for novel biomarkers and new designs as well as delivery methods of targeted agents are fueling the next wave of advances in cancer therapy. Keywords: Biomarker, Tumor-associated antigen, BiTE, Antibody-drug conjugate, CAR-T Tumor-associated antigens (TAA) or cancer biomarkers including coltuximab ravtansine (SAR3419), denintuzu- are major targets for cancer therapies.
    [Show full text]
  • HAMP - Health Alliance Medical Plan – Commercial
    HAMP - Health Alliance Medical Plan – Commercial HAMP - Health Alliance Primary Alt Descriptions HCPCS Codes Medical Plan - Administration Technique Drug Class Commercial 5-Fluorouracil 5FU, Adrucil J9190 Y INJECTABLE Primary Ado-Trastuzumab Emtansine Kadcyla J9354 Y INJECTABLE Primary Aldesleukin Proleukin, Interleukin-2 J9015 Y INJECTABLE Primary Arsenic Trioxide Trisenox J9017 Y INJECTABLE Primary Asparaginase Erwinaze J9019 Y INJECTABLE Primary Atezolizumab Tecentriq J9022 Y INJECTABLE Primary Avelumab Bavencio J9023 Y INJECTABLE Primary Azacitidine Vidaza J9025 Y INJECTABLE Primary BCG TheraCys, Tice J9031 Y INJECTABLE Primary Belinostat Beleodaq J9032 Y INJECTABLE Primary Bendamustine Bendamustine (Not otherwise specified) C9399 Y INJECTABLE Primary Bendamustine Bendamustine (Not otherwise specified) J9999 Y INJECTABLE Primary Bendamustine Treanda J9033 Y INJECTABLE Primary Bendamustine HCL Belrapzo C9042 Y INJECTABLE Primary Bendamustine HCL Bendeka J9034 Y INJECTABLE Primary Bevacizumab Avastin J9035 Y INJECTABLE Primary Bevacizumab-awwb (not currently Mvasi Q5107 Y INJECTABLE Primary available on the market) Bleomycin Blenoxane J9040 Y INJECTABLE Primary Blinatumomab Blincyto J9039 Y INJECTABLE Primary Bortezomib Velcade J9041 Y INJECTABLE Primary Bortezomib Bortezomib (not otherwise specified) J9044 Y INJECTABLE Primary Brentuximab Vedotin Adcetris J9042 Y INJECTABLE Primary Cabazitaxel Jevtana J9043 Y INJECTABLE Primary Calaspargase pegol-mknl Asparlas J3490 Y INJECTABLE Primary Calaspargase pegol-mknl Asparlas J3590 Y INJECTABLE
    [Show full text]