DOCSLIB.ORG

A Phase 1B/2 Study of Ramucirumab in Combination with Emibetuzumab in Patients with Advanced Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. A Phase 1b/2 Study of Ramucirumab in Combination with Emibetuzumab in Patients with Advanced Cancer James J. Harding1,2, Andrew X. Zhu3, Todd M. Bauer4, Toni K. Choueiri5, Alexander Drilon1,2, Martin H. Voss1,2, Charles Fuchs5, Ghassan K. Abou-Alfa1,2, Sameera Wijayawardana6, Xuejing A Wang6, Brian Moser6 Arantxa Uruñuela6, Volker Wacheck6, Johanna Bendell4 1 Memorial Sloan Kettering Cancer Center New York, New York 2 Weill Cornell Medical College, New York, New York 3Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts4 4Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee 5Yale Cancer Center, Smilow Cancer Hospital, New Haven, Connecticut 6Eli Lilly and Company, Indianapolis, Indiana Running Title: Phase 1b/2 of ramucirumab plus emibetuzumab Keywords: Antibodies, phase Ib/2, emibetuzumab plus ramucirumab, MET protein, advanced or metastatic cancers. Conflicts of Interest: J.J.H was in part supported through the NIH/NCI Cancer Center Support Grant P30 CA008748. J.J.H has received consulting fees from Bristol Myers Squibb, Eli Lilly, CytomX, and Eisai, and research funds from Bristol Myers Squibb. C.S.F. reports consulting role for Agios, Bain Capital, Bayer, Celgene, Dicerna, Five Prime Therapeutics, Gilead Sciences, Eli Lilly, Entrinsic Health, Genentech, KEW, Merck, Merrimack Pharmaceuticals, Pfizer, Sanofi, Taiho, and Unum Therapeutics. He also serves as a Director for CytomX Therapeutics and owns unexercised stock options for CytomX and Entrinsic Health. A.E.D. received honoraria from Medscape, OncLive, PeerVoice, Physicians Education Resources, Tyra Biosciences, Targeted Oncology, MORE Health, Research to Practice, Foundation Medicine, Peerview, AstraZeneca, Genentech/Roche, Bayer; Consulting and Advisory role in Ignyta, Loxo, TP Therapeutics, AstarZeneca, Pfizer, Blueprint Medicines, Genentech/Roche, Takeda, Helsinn Therapeutics, BeiGene, Hengrui Therapeutics, Exelixis and Bayer. SW, XAW, BM, AU and VW are employees and shareholders of Eli Lilly and Company. This study was funded by Eli Lilly and Company. 1 Downloaded from clincancerres.aacrjournals.org on September 26, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Corresponding author James J. Harding Address: 300 East 66th Street Memorial Sloan Kettering Cancer Center, New York, Untied States of America. Phone: 646-888-4314 Fax: 646-888-4255 E-mail: [email protected] Target journal: Clinical Cancer Research 2 Downloaded from clincancerres.aacrjournals.org on September 26, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Statement of Translational Relevance: Mesenchymal epithelial transition factor proto-oncogene receptor tyrosine kinase (MET) signaling supports oncogenic processes including cell proliferation, invasion, and metastasis. MET activation also contributes to resistance to VEGF/VEGFR targeting agents. This phase 1b/2 study demonstrates a favorable safety profile for emibetuzumab, a humanized, bivalent monoclonal antibody targeting MET, when administered with the VEGFR2 antibody ramucirumab. Exploratory data suggest that baseline tumoral MET expression is associated with clinical anti-tumor activity for this combination in HCC. Patients with high MET expression exhibited an approximate 3-fold longer PFS relative to HCC patients with low MET expression. Given the negative prognosis associated with MET-high HCCs (1), the median PFS of 8.1 months observed herein is of interest as it exceeds previously reported median PFS of 2.0 months for MET high HCC patients treated with MET targeted therapy (2). These translational data warrant additional studies to investigate MET inhibition as an antiangiogenic treatment in HCC. Word count: (current 149/max 150 words) 3 Downloaded from clincancerres.aacrjournals.org on September 26, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Abstract: Purpose: Inhibition of the vascular endothelial growth factor receptor-2 (VEGFR-2) blocks angiogenesis and attenuates tumor growth, but cancers may evade this effect through activation of the hepatocyte growth factor (HGF) receptor MET. Here we report results of the phase 1b/2 study of ramucirumab, a monoclonal anti-VEGFR-2 antibody, plus the anti-MET monoclonal antibody emibetuzumab. Patients and Methods: A 3+3 dose escalation of emibetuzumab plus ramucirumab (Phase 1b) was followed by tumor-specific expansion cohorts. Primary objectives were to determine the recommended phase 2 dose (RP2D) and to evaluate antitumor activity. Secondary objectives included safety, pharmacokinetics, and immunogenicity. Tumoral MET expression was explored by immunohistochemistry. Results: 97 solid tumor patients (6 phase 1b, 16 GEJ, 45 HCC, 15 RCC, and 15 NSCLC) received emibetuzumab at 750 or 2000 mg flat dosing plus ramucirumab at 8mg/kg Q2W. No DLTs were observed. Common AEs were primarily mild or moderate and included fatigue (36.1%), peripheral edema (28.9%), and nausea (14.4%). Emibetuzumab exposures were similar as in previous studies with no apparent drug-drug interactions. Five partial responses (5.2%) were observed across all tumor types. The greatest anti- tumor activity was noted in HCC with a 6.7% ORR, 60% DCR, and 5.42 months (95% CI: 1.64-8.12) PFS. HCC with high MET expression showed improved PFS with approximately threefold increase in PFS (8.1 vs. 2.8 months) relative to low MET expression. 4 Downloaded from clincancerres.aacrjournals.org on September 26, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Conclusions: Ramucirumab plus emibetuzumab was safe and exhibited cytostatic antitumor activity. MET expression may help to select patients benefitting most from this combination treatment in select tumor types. Word count: 250 words (max 250 words) 5 Downloaded from clincancerres.aacrjournals.org on September 26, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. INTRODUCTION Vascular endothelial growth factor (VEGF) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) have critical roles in the physiologic growth and maintenance of blood vessels. High levels of VEGF and other angiogenic factors are often associated with an increased level of tumor microvessel density, aggressive pathologic features, and poor clinical outcomes in a variety of cancer histology. In preclinical models, blockade of the VEGF/VEGFR-2 axis leads to tumor vascular remodeling and cancer cell death. Pathological dysregulation of angiogenesis is an established hallmark of malignancy, and both VEGFR-2 and its ligand are bona fide therapeutic targets either with selective monoclonal antibodies or via multi-targeted tyrosine kinase inhibitors, in a variety of tumor types, including non-small lung cancer (NSCLC), ovarian cancer, renal cell carcinoma (RCC), and several gastrointestinal malignancies such as colorectal cancer (CRC), gastric or gastroesophageal junction adenocarcinoma (GEJ), and hepatocellular carcinoma (HCC) (3-6). Innate and acquired resistance to anti-angiogenic therapy is frequent and multi- factorial, but is in part mediated by the hepatocyte growth factor (HGF) receptor MET (7- 9). Both ligand-dependent and -independent MET activation is implicated in tumor cell motility, proliferation, survival, invasion, metastasis, and angiogenesis. Indeed, the MET receptor is overexpressed, activated, amplified, or mutated in a wide variety of solid tumors (9-11), and contributes to an aggressive tumor biology (12,13). Importantly, VEGF blockade leads to a reciprocal increase in MET concentration and activation (8), which in turn leads to MET-mediated anti-angiogenic escape (14). Simultaneous pharmacological inhibition of MET and VEGF signaling mitigates MET-mediated escape, thereby slowing 6 Downloaded from clincancerres.aacrjournals.org on September 26, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on May 29, 2019; DOI: 10.1158/1078-0432.CCR-18-4010 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. tumor growth and reducing invasion and metastasis (14). Thus, there is compelling preclinical evidence to support co-targeting VEGF and MET pathways in malignances to enhance the activity of VEGF/VEGFR-2 monotherapy. Clinically the concept MET as a mechanism of anti-angiogenic resistance is also suggested in several correlative programs across multiple tumor types indicating
Recommended publications
  • Lung Cancer Drugs in the Pipeline

    Lung Cancer Drugs in the Pipeline

    HemOnc today | JANUARY 10, 2016 | Healio.com/HemOnc 5 Lung Cancer Drugs in the Pipeline HEMONC TODAY presents this guide to drugs in phase 2 or phase 3 development for lung cancer-related indications. Clinicians can use this chart as a quick reference to learn about the status of those drugs that may be clinically significant to their practice. Generic name (Brand name, Manufacturer) Indication(s) Development status abemaciclib (Eli Lilly) non–small cell lung cancer phase 3 ABP 215 (Allergan/Amgen) non–small cell lung cancer (advanced disease) phase 3 ACP-196 (Acerta Pharma) non–small cell lung cancer (advanced disease) phase 2 ado-trastuzumab emtansine (Kadcyla, Genentech) non–small cell lung cancer (HER-2–positive disease) phase 2 afatinib (Gilotrif, Boehringer Ingelheim) lung cancer (squamous cell carcinoma) phase 3 aldoxorubicin (CytRx) small cell lung cancer phase 2 alectinib (Alecensa, Genentech) non–small cell lung cancer (second-line treatment of ALK-positive disease) phase 2 non–small cell lung cancer (first-line treatment of ALK-positive disease); phase 3 alisertib (Takeda) malignant mesothelioma, small cell lung cancer phase 2 avelumab (EMD Serono/Pfizer) non–small cell lung cancer phase 3 AZD9291 (AstraZeneca) non–small cell lung cancer (first-line treatment of advancedEGFR -positive disease; phase 3 second-line treatment of advanced EGFR-positive, T790M-positive disease) bavituximab (Peregrine Pharmaceuticals) non–small cell lung cancer (previously treated advanced/metastatic disease) phase 3 belinostat (Beleodaq, Spectrum
  • Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies

    Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies

    Predictive QSAR tools to aid in early process development of monoclonal antibodies John Micael Andreas Karlberg Published work submitted to Newcastle University for the degree of Doctor of Philosophy in the School of Engineering November 2019 Abstract Monoclonal antibodies (mAbs) have become one of the fastest growing markets for diagnostic and therapeutic treatments over the last 30 years with a global sales revenue around $89 billion reported in 2017. A popular framework widely used in pharmaceutical industries for designing manufacturing processes for mAbs is Quality by Design (QbD) due to providing a structured and systematic approach in investigation and screening process parameters that might influence the product quality. However, due to the large number of product quality attributes (CQAs) and process parameters that exist in an mAb process platform, extensive investigation is needed to characterise their impact on the product quality which makes the process development costly and time consuming. There is thus an urgent need for methods and tools that can be used for early risk-based selection of critical product properties and process factors to reduce the number of potential factors that have to be investigated, thereby aiding in speeding up the process development and reduce costs. In this study, a framework for predictive model development based on Quantitative Structure- Activity Relationship (QSAR) modelling was developed to link structural features and properties of mAbs to Hydrophobic Interaction Chromatography (HIC) retention times and expressed mAb yield from HEK cells. Model development was based on a structured approach for incremental model refinement and evaluation that aided in increasing model performance until becoming acceptable in accordance to the OECD guidelines for QSAR models.
  • USAN Naming Guidelines for Monoclonal Antibodies |

    USAN Naming Guidelines for Monoclonal Antibodies |

    Monoclonal Antibodies In October 2008, the International Nonproprietary Name (INN) Working Group Meeting on Nomenclature for Monoclonal Antibodies (mAb) met to review and streamline the monoclonal antibody nomenclature scheme. Based on the group's recommendations and further discussions, the INN Experts published changes to the monoclonal antibody nomenclature scheme. In 2011, the INN Experts published an updated "International Nonproprietary Names (INN) for Biological and Biotechnological Substances—A Review" (PDF) with revisions to the monoclonal antibody nomenclature scheme language. The USAN Council has modified its own scheme to facilitate international harmonization. This page outlines the updated scheme and supersedes previous schemes. It also explains policies regarding post-translational modifications and the use of 2-word names. The council has no plans to retroactively change names already coined. They believe that changing names of monoclonal antibodies would confuse physicians, other health care professionals and patients. Manufacturers should be aware that nomenclature practices are continually evolving. Consequently, further updates may occur any time the council believes changes are necessary. Changes to the monoclonal antibody nomenclature scheme, however, should be carefully considered and implemented only when necessary. Elements of a Name The suffix "-mab" is used for monoclonal antibodies, antibody fragments and radiolabeled antibodies. For polyclonal mixtures of antibodies, "-pab" is used. The -pab suffix applies to polyclonal pools of recombinant monoclonal antibodies, as opposed to polyclonal antibody preparations isolated from blood. It differentiates polyclonal antibodies from individual monoclonal antibodies named with -mab. Sequence of Stems and Infixes The order for combining the key elements of a monoclonal antibody name is as follows: 1.
  • Monoclonal Antibody Playbook

    Monoclonal Antibody Playbook

    Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide Outpatient administration guide for healthcare providers 2 SEPTEMBER 2021 1 Introduction to COVID-19 Monoclonal Antibody Therapy 2 Overview of Emergency Use Authorizations 3 Site and Patient Logistics Site preparation Patient pathways to monoclonal administration 4 Team Roles and Responsibilities Leadership Administrative Clinical Table of 5 Monoclonal Antibody Indications and Administration Indications Contents Preparation Administration Response to adverse events 6 Supplies and Resources Infrastructure Administrative Patient Intake Administration 7 Examples: Sites of Administration and Staffing Patterns 8 Additional Resources 1 1. Introduction to Monoclonal Therapy 2 As of 08/13/21 Summary of COVID-19 Therapeutics 1 • No Illness . Health, no infections • Exposed Asymptomatic Infected . Scope of this Implementation Guide . Not hospitalized, no limitations . Monoclonal Antibodies for post-exposure prophylaxis (Casirivimab + Imdevimab (RGN)) – EUA Issued. • Early Symptomatic . Scope of this Implementation Guide . Not hospitalized, with limitations . Monoclonal Antibodies for treatment (EUA issued): Bamlanivimab + Etesevimab1 (Lilly) Casirivimab + Imdevimab (RGN) Sotrovimab (GSK/Vir) • Hospital Adminission. Treated with Remdesivir (FDA Approved) or Tocilizumab (EUA Issued) . Hospitalized, no acute medical problems . Hospitalized, not on oxygen . Hospitlaized, on oxygen • ICU Admission . Hospitalized, high flow oxygen, non-invasive ventilation
  • REGENERON PHARMACEUTICALS, INC. (Exact Name of Registrant As Specified in Charter)

    REGENERON PHARMACEUTICALS, INC. (Exact Name of Registrant As Specified in Charter)

    UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 9, 2017 (February 9, 2017) REGENERON PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in Charter) New York 000-19034 13-3444607 (State or other jurisdiction (Commission (IRS Employer of Incorporation) File No.) Identification No.) 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 (Address of principal executive offices, including zip code) (914) 847-7000 (Registrant's telephone number, including area code) Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions: ☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) ☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) ☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) ☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) Item 2.02 Results of Operations and Financial Condition. On February 9, 2017, Regeneron Pharmaceuticals, Inc. issued a press release announcing its financial and operating results for the quarter and year ended December 31, 2016. A copy of the press release is being furnished to the Securities and Exchange Commission as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference to this Item 2.02.
  • The Future of Antibodies As Cancer Drugs

    The Future of Antibodies As Cancer Drugs

    REVIEWS Drug Discovery Today Volume 17, Numbers 17/18 September 2012 The biopharmaceutical industry’s pipeline of anticancer antibodies includes 165 candidates with substantial diversity in composition, targets and mechanisms of action that hold promise to be the cancer drugs of the future. Reviews FOUNDATION REVIEW Foundation review: The future of antibodies as cancer drugs 1 2 Dr Janice Reichert Janice M. Reichert and Eugen Dhimolea is Research Assistant Professor at Tufts 1 Center for the Study of Drug Development, Tufts University School of Medicine, 75 Kneeland Street, University’s Center for the Study of Drug Development Suite 1100, Boston, MA 02111, USA 2 (CSDD). She is also Founder Department of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, 77 Louis Pasteur Ave., and Editor-in-Chief of mAbs, Harvard Institutes of Medicine, Room 309, Boston, MA 02215, USA a peer-reviewed, PubMed- indexed biomedical journal that focuses on topics relevant to antibody research Targeted therapeutics such as monoclonal antibodies (mAbs) have proven and development; President of the board of directors of The Antibody Society; and a member of the board successful as cancer drugs. To profile products that could be marketed in of the Peptide Therapeutics Foundation. At CSDD, the future, we examined the current commercial clinical pipeline of mAb Dr Reichert studies innovation in the pharmaceutical and biotechnology industries. Her work focuses on candidates for cancer. Our analysis revealed trends toward development of strategic analyses of investigational candidates and marketed products, with an emphasis on the clinical a variety of noncanonical mAbs, including antibody–drug conjugates development and approval of new therapeutics and (ADCs), bispecific antibodies, engineered antibodies and antibody vaccines.
  • CYRAMZA (Ramucirumab) Injection Label

    CYRAMZA (Ramucirumab) Injection Label

    1 HIGHLIGHTS OF PRESCRIBING INFORMATION • 500 mg/50 mL (10 mg per mL) solution, single-dose vial (3) These highlights do not include all the information needed to use CYRAMZA safely and effectively. See full prescribing information ------------------------------- CONTRAINDICATIONS ------------------------------ for CYRAMZA. None CYRAMZA (ramucirumab) injection, for intravenous infusion ------------------------ WARNINGS AND PRECAUTIONS ----------------------- Initial U.S. Approval: 2014 • Arterial Thromboembolic Events (ATEs): Serious, sometimes fatal WARNING: HEMORRHAGE ATEs have been reported in clinical trials. Discontinue CYRAMZA for severe ATEs. (5.2) See full prescribing information for complete boxed warning. • Hypertension: Monitor blood pressure and treat hypertension. CYRAMZA increased the risk of hemorrhage, including severe Temporarily suspend CYRAMZA for severe hypertension. and sometimes fatal hemorrhagic events. Permanently Discontinue CYRAMZA for hypertension that cannot be medically discontinue CYRAMZA in patients who experience severe controlled. (5.3) bleeding [see Dosage and Administration (2.3), Warnings and • Infusion-Related Reactions: Monitor for signs and symptoms Precautions (5.1)]. during infusion. (5.4) • Gastrointestinal Perforation: Discontinue CYRAMZA. (5.5) --------------------------- RECENT MAJOR CHANGES -------------------------- • Impaired Wound Healing: Withhold CYRAMZA prior to surgery. Indications and Usage 11/2014 (5.6) • Clinical Deterioration in Patients with Cirrhosis: New onset or Dosage and Administration:
  • COVID-19 Immunotherapy: Novel Humanized 47D11 Monoclonal Antibody

    COVID-19 Immunotherapy: Novel Humanized 47D11 Monoclonal Antibody

    Review Article ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2020.29.004828 COVID-19 Immunotherapy: Novel Humanized 47D11 Monoclonal Antibody Basma H Marghani* Department of Physiology, Faculty of Veterinary Medicine, Mansoura University, Egypt *Corresponding author: Basma H Marghani, Department of Physiology, Faculty of Veterinary Medicine, Mansoura University, Egypt ARTICLE INFO ABSTRACT Received: August 10, 2020 Published: August 18, 2020 rapidly to the other countries all over the world, caused a novel Coronavirus-2019 (COV- SARS-CoV-2 was appeared firstly in Wuhan, China in December 2019, then spread- gency. After infection, virus entry the host cell through spike proteins (S)- angiotensin Citation: Basma H Marghani. COVID-19 ID-19). The World Health Organization was branded COVID-19 as a global health emer Immunotherapy: Novel Humanized 47D11 converting enzyme 2 (ACE2) cell membrane receptor via their S-Binding domain, then Monoclonal Antibody. Biomed J Sci & Tech virus replication caused acute respiratory disease syndrome (ARDS). Till now there was Res 29(4)-2020. BJSTR. MS.ID.004828. no vaccines or anti-viral drugs for coronavirus infection. One effective treatment is the use of human monoclonal antibodies (mAbs) which are engineered to target and block Keywords: COVID-19; Immunotherapy; cell surface receptor. mAbs could be given to people in the early stages of COVID-19 as a Full-Length Humanized Monoclonal Anti- therapeutic, or used prophylactically to give immediate, long-term immunity to vulnera- bodies; ACE Inhibitor ble people such as healthcare workers. The neutralizing humanized 47D11 monoclonal antibody targets a common epitope on SARS-CoV2 virus and may offer potential for pre- Abbreviations: ACE2: Angiotensin-Con- vention and treatment of COVID-19.89U (Graphical Abstract 1).
  • 2017 Immuno-Oncology Medicines in Development

    2017 Immuno-Oncology Medicines in Development

    2017 Immuno-Oncology Medicines in Development Adoptive Cell Therapies Drug Name Organization Indication Development Phase ACTR087 + rituximab Unum Therapeutics B-cell lymphoma Phase I (antibody-coupled T-cell receptor Cambridge, MA www.unumrx.com immunotherapy + rituximab) AFP TCR Adaptimmune liver Phase I (T-cell receptor cell therapy) Philadelphia, PA www.adaptimmune.com anti-BCMA CAR-T cell therapy Juno Therapeutics multiple myeloma Phase I Seattle, WA www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 "armored" CAR-T Juno Therapeutics recurrent/relapsed chronic Phase I cell therapy Seattle, WA lymphocytic leukemia (CLL) www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 CAR-T cell therapy Intrexon B-cell malignancies Phase I Germantown, MD www.dna.com ZIOPHARM Oncology www.ziopharm.com Boston, MA anti-CD19 CAR-T cell therapy Kite Pharma hematological malignancies Phase I (second generation) Santa Monica, CA www.kitepharma.com National Cancer Institute Bethesda, MD Medicines in Development: Immuno-Oncology 1 Adoptive Cell Therapies Drug Name Organization Indication Development Phase anti-CEA CAR-T therapy Sorrento Therapeutics liver metastases Phase I San Diego, CA www.sorrentotherapeutics.com TNK Therapeutics San Diego, CA anti-PSMA CAR-T cell therapy TNK Therapeutics cancer Phase I San Diego, CA www.sorrentotherapeutics.com Sorrento Therapeutics San Diego, CA ATA520 Atara Biotherapeutics multiple myeloma, Phase I (WT1-specific T lymphocyte South San Francisco, CA plasma cell leukemia www.atarabio.com
  • The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer

    The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer

    Journal of Clinical Medicine Review The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer Ramon Andrade De Mello 1,2,3,* , Nathália Moisés Neves 2 , Giovanna Araújo Amaral 2, Estela Gudin Lippo 4, Pedro Castelo-Branco 1, Daniel Humberto Pozza 5 , Carla Chizuru Tajima 6 and Georgios Antoniou 7 1 Algarve Biomedical Centre, Department of Biomedical Sciences and Medicine University of Algarve (DCBM UALG), 8005-139 Faro, Portugal; [email protected] 2 Division of Medical Oncology, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo 04037-004, Brazil; [email protected] (N.M.N.); [email protected] (G.A.A.) 3 Precision Oncology and Health Economics Group (ONCOPRECH), Post-Graduation Program in Medicine, Nine of July University (UNINOVE), São Paulo 01525-000, Brazil 4 School of Biomedical Sciences, Santo Amaro University, São Paulo 01525-000, Brazil; [email protected] 5 Department of Biomedicine & I3S, Faculty of Medicine, University of Porto (FMUP), 4200-317 Porto, Portugal; [email protected] 6 Hospital São José & Hospital São Joaquim, A Beneficência Portuguesa de São Paulo, São Paulo 01323-001, Brazil; [email protected] 7 Division of Medical Oncology, Mount Vernon Cancer Center, London HA6 2RN, UK; [email protected] * Correspondence: [email protected] Received: 15 May 2020; Accepted: 10 June 2020; Published: 19 June 2020 Abstract: Introduction: Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients. Methods: We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and NSCLC.
  • Coverage of Monoclonal Antibody Products to Treat COVID-19

    Coverage of Monoclonal Antibody Products to Treat COVID-19

    Coverage of Monoclonal Antibody Products to Treat COVID-19 Monoclonal antibody products to treat Coronavirus disease 2019 (COVID-19) help the body fight the virus or slow the virus’s growth. Medicare beneficiaries have coverage without beneficiary cost sharing for these products when used as authorized or approved by the Food and Drug Administration (FDA). Disclaimer: The contents of this document do not have the force and effect of law and are not meant to bind the public Medicare in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. This communication was printed, published, or produced and disseminated at U.S. taxpayer expense. Site of Care1 Payable by Expected Patient Expected Payment to Providers: Medicare Cost-Sharing Key Facts • Medicare payment for monoclonal antibody products to treat COVID-19 is similar across Inpatient No patient sites of care, with some small differences. Hospital cost-sharing • Medicare pays for the administration of monoclonal antibody products to treat COVID-19. For example, beginning on May 6, 2021, Medicare will pay approximately Outpatient $450 in most settings, or approximately $750 No patient in the beneficiary’s home or residence, for Hospital or cost-sharing the administration of certain monoclonal “Hospital 4 2 antibody products to treat COVID-19. For without Walls ” monoclonal antibody products to treat COVID-19 that are administered before May 6, 2021, the Medicare payment rate in all No patient settings is approximately $310. Outpatient cost-sharing3 Physician Office/ • CMS will exercise enforcement discretion to Infusion Center allow Medicare-enrolled immunizers working within their scope of practice and subject to applicable state law to bill directly and receive direct reimbursement from the Medicare program for administering Nursing Home monoclonal antibody treatments to No patient (See third bullet in Medicare Part A Skilled Nursing Facility Key Facts on CMS cost-sharing residents.
  • An EANM Procedural Guideline

    An EANM Procedural Guideline

    European Journal of Nuclear Medicine and Molecular Imaging https://doi.org/10.1007/s00259-018-4052-x GUIDELINES Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline A. Signore1 & F. Jamar2 & O. Israel3 & J. Buscombe4 & J. Martin-Comin5 & E. Lazzeri6 Received: 27 April 2018 /Accepted: 6 May 2018 # The Author(s) 2018 Abstract Introduction Radiolabelled autologous white blood cells (WBC) scintigraphy is being standardized all over the world to ensure high quality, specificity and reproducibility. Similarly, in many European countries radiolabelled anti-granulocyte antibodies (anti-G-mAb) are used instead of WBC with high diagnostic accuracy. The EANM Inflammation & Infection Committee is deeply involved in this process of standardization as a primary goal of the group. Aim The main aim of this guideline is to support and promote good clinical practice despite the complex environment of a national health care system with its ethical, economic and legal aspects that must also be taken into consideration. Method After the standardization of the WBC labelling procedure (already published), a group of experts from the EANM Infection & Inflammation Committee developed and validated these guidelines based on published evidences. Results Here we describe image acquisition protocols, image display procedures and image analyses as well as image interpre- tation criteria for the use of radiolabelled WBC and monoclonal antigranulocyte antibodies. Clinical application for WBC and anti-G-mAb scintigraphy is also described. Conclusions These guidelines should be applied by all nuclear medicine centers in favor of a highly reproducible standardized practice. Keywords Infection .