DOCSLIB.ORG

Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval Date: 08-Jul-2019

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval Date: 08-Jul-2019 Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval date: 08-Jul-2019 TWO-ARM PARALLEL PHASE 2 CLINICAL TRIAL OF ATEZOLIZUMAB WITH/WITHOUT LOW DOSE, LOCAL RADIOTHERAPY (2 X 2GY) IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED STAGE FOLLICULAR LYMPHOMA PROTOCOL FACE PAGE FOR MSK THERAPEUTIC/DIAGNOSTIC PROTOCOL Principal Investigator/Department: M. Lia Palomba, MD Medicine/Lymphoma Co-Principal Andrew Zelenetz, MD, PhD Medicine/Lymphoma Investigator(s)/Department: Joachim Yahalom, MD Radiation Oncology Investigator(s)/Department: Batlevi, Connie, MD, PhD Medicine/Lymphoma Hamlin, Paul, MD Medicine/Lymphoma Horwitz, Steven, MD Medicine/Lymphoma Joffe, Erel, MD Medicine/Lymphoma Kumar, Anita, MD Medicine/Lymphoma Matasar, Matthew, MD Medicine/Lymphoma Moskowitz, Alison, MD Medicine/Lymphoma Noy, Ariela, MD Medicine/Lymphoma Straus, David, MD Medicine/Lymphoma Younes, Anas, MD Medicine/Lymphoma Rodriguez-Rivera, Ildefonso, MD Medicine/Lymphoma Von Keudell, Gottfried, MD Medicine/Lymphoma Gorsky, Mila, MD Medicine/Regional Networks Hamilton, Audrey, MD Medicine/Regional Networks Korde, Neha, MD Medicine/Regional Networks Ligresti, Louise, MD MedicineRegional Networks Owens, Colette, MD MedicineRegional Networks Danila, Daniel, MD Medicine/Genitourinary Onc Mauro, Michael, MD Medicine/Leukemia Gu, Ping, MD Medicine/Genitourinary Onc Mauro, Michael, MD Medicine/Leukemia Preeshagul, Isabel, MD Medicine/Thoracic Onc Wang, Rui, MD Medicine Aghalar, Jahan, MD Medicine/Genitourinary Onc Desai, Avni, MD Medicine/Gastrointestinal Onc Lahoud, Oscar, MD Medicine/Marrow Transplant Mailankody, Sham, MBBS Medicine/Cellular Therapeutics Center (CTC) Page 1 of 115 Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval date: 08-Jul-2019 Korde, Neha, MD Medicine/Regional Networks Klimek, Virginia, MD Medicine/Leukemia Konner, Jason, MD Medicine/Gynecologic Medical Oncology Service Namakydoust, Azadeh, MD Medicine Shcherba, Marina, DO Regional Networks Apollo, Arlyn, MD Med/Regional Networks Goldberg, Zoe, MD Med/Regional Networks Ng, Kenneth, MD Med/Regional Networks Troso-Sandoval, Tiffany, MD Med/Regional Networks Caron, Philip, MD, PhD Med/Regional Networks Hassoun, Hani, MD Med/Regional Networks Momtaz, Parisa, MD Medicine/Melanoma and Immunotherapeutics Service Bilger, Ashley, PA Medicine/Lymphoma Davey, Theresa, PA Medicine/Lymphoma Duggan, Tara, NP Nursing Hancock, Helen, NP Nursing Rose, Georgia, NP Nursing Schreiber, Jillian, PA Medicine/Lymphoma Ames, Ashley, NP Nursing Devin, Callan, RN Nursing Carter, Jason, PA Medicine/Lymphoma Depaola, Nadia, PA Medicine/Lymphoma McCall, Susan, NP Nursing Schreiber, Jillian, PA Medicine/Lymphoma Palumbo, Teresa, PA Medicine/Lymphoma Dogan, Ahmet, MD, PhD Pathology Dept & Molecular Div Getrajdman, George, MD Radiology/Interventional Radiology Serv Girshman, Jeffrey, MD Radiology Peled, Jonathan, MD Graduate Medical Education Grewal, Ravinder, MD Radiology Byrne, Regina, NP Nursing Matthews, Leslie, NP Nursing O'Connor, Katherine, NP Nursing Wisniewski, Michelle, PA Nursing Pierre, Amy, NP Nursing Arnell, Geri, RN Nursing Cogswell, Janet, RN Nursing Heinz, Nicole, RN Nursing Kelly, Irene, RN Nursing Page 2 of 115 Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval date: 08-Jul-2019 Kennedy, Maureen, RN Nursing Langish, Raylene, RN Nursing Mar-Chaim, Sherie, RN Nursing Pierre, Amy, NP Nursing Consenting Aghalar, Jahan, MD Medicine/Genitourinary Onc Professional(s)/Department: Apollo, Arlyn, MD Med/Regional Networks Batlevi, Connie, MD, PhD Medicine/Lymphoma Caron, Philip, MD, PhD Med/Regional Networks Desai, Avni, MD Medicine/Gastrointestinal Onc Goldberg, Zoe, MD Med/Regional Networks Gorsky, Mila, MD Med/Regional Networks Gu, Ping, MD Medicine/Genitourinary Onc Hamilton, Audrey, MD Med/Regional Networks Hamlin, Paul, MD Medicine/Lymphoma Hassoun, Hani, MD Med/Regional Networks Horwitz, Steven, MD Medicine/Lymphoma Joffe, Erel, MD Medicine/Lymphoma Klimek, Virginia, MD Medicine/Leukemia Konner, Jason, MD Medicine/Gynecologic Medical Oncology Service Kriplani, Anuja, MD Graduate Medical Education Kumar, Anita, MD Medicine/Lymphoma Lahoud, Oscar, MD Medicine/Marrow Transplant Ligresti, Louise, MD Regional Networks Mailankody, Sham, MBBS Medicine/Cellular Therapeutics Center (CTC) Matasar, Matthew, MD Medicine/Lymphoma Moskowitz, Alison, MD Medicine/Lymphoma Namakydoust, Azadeh, MD Medicine Ng, Kenneth, MD Med/Regional Networks Noy, Ariela, MD Medicine/Lymphoma Owens, Colette, MD Medicine/Lymphoma Palomba, M. Lia, MD Medicine/Lymphoma Shcherba, Marina, DO Regional Networks Straus, David, MD Medicine/Lymphoma Troso-Sandoval, Tiffany, MD Med/Regional Networks Younes, Anas, MD Medicine/Lymphoma Zelenetz, Andrew, MD, PhD Medicine/Lymphoma Danila, Daniel, MD Medicine/Genitourinary Onc Gu, Ping, MD Medicine/Gastrointestinal Onc Kriplani, Anuja, MD Medicine Medicine/Leukemia Mauro, Michael, MD Medicine/Melanoma and Momtaz, Parisa, MD Immunotherapeutics Service Medicine/Thoracic Onc Preeshagul, Isabel, DO Medicine/Lymphoma Rodriguez-Revira, Ildefonso, MD Medicine/Lymphoma Von Keudell, Gottfried, MD Page 3 of 115 Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval date: 08-Jul-2019 Wang, Rui, MD Medicine Please Note: A Consenting Professional must have completed the mandatory Human Subjects Education and Certification Program. OneMSK Sites Manhattan Basking Ridge Westchester Nassau Commack Monmouth Bergen Memorial Sloan Kettering Cancer Center 1275 York Avenue New York, New York 10065 Page 4 of 115 Memorial Sloan Kettering Cancer Center IRB Number: 17-360 A(4) Approval date: 08-Jul-2019 Table of Contents 1.0 PROTOCOL SUMMARY AND/OR SCHEMA ......................................................................... 9 2.0 OBJECTIVES AND SCIENTIFIC AIMS ................................................................................ 10 2.1 Primary Objectives................................................................................................................. 10 2.2 Secondary Objectives ............................................................................................................ 11 3.0 BACKGROUND AND RATIONALE ..................................................................................... 11 3.1 Natural History and Current Management of Follicular Lymphoma ........................................ 11 3.2 Radiotherapy Background...................................................................................................... 12 3.3.1 Summary of Nonclinical Experience ................................................................................ 14 3.3.2 Clinical Experience with Atezolizumab............................................................................. 15 4.0 OVERVIEW OF STUDY DESIGN/INTERVENTION.............................................................. 18 4.1 Design............................................................................................................................... 18 4.1.1 Rationale for Patient Population ...................................................................................... 18 4.1.2 Rationale for Atezolizumab Starting Dose and Schedule ................................................. 18 4.1.3 Rationale for Radiotherapy Dose and Schedule .............................................................. 19 4.1.4 Rationale for Potential Treatment Beyond Progression ................................................... 19 4.2 Intervention ....................................................................................................................... 20 5.0 THERAPEUTIC/DIAGNOSTIC AGENTS ............................................................................. 20 5.1 Study Drug: ATEZOLIZUMAB............................................................................................... 20 5.1.1 Formulation ..................................................................................................................... 20 5.1.2 Dosage Administration, and Storage ............................................................................... 20 5.2 Low- Dose, Local Radiotherapy ............................................................................................ 21 5.2.1 Simulation ....................................................................................................................... 21 5.2.2 Treatment Planning ......................................................................................................... 21 5.2.3 Treatment Delivery (LINAC- based)................................................................................. 23 5.2.4 Study Medication Accountability ...................................................................................... 23 6.0 CRITERIA FOR SUBJECT ELIGIBILITY ............................................................................. 23 6.1 Subject Inclusion Criteria................................................................................................... 23 6.2 Subject Exclusion Criteria ................................................................................................. 25 General Exclusion Criteria: .......................................................................................................... 25 7.0 RECRUITMENT PLAN ......................................................................................................... 28 8.0 PRETREATMENT EVALUATION .......................................................................................
Load more

Recommended publications
  • 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.
    [Show full text]
  • Development of Red Blood Cell Autoantibodies Following Treatment with Checkpoint Inhibitors
    CASE R EP O RT Development of red blood cell autoantibodies following treatment with checkpoint inhibitors: a new class of anti-neoplastic, immunotherapeutic agents associated with immune dysregulation L.L.W. Cooling, J. Sherbeck, J.C. Mowers, and S.L. Hugan Ipilimumab, nivolumab, and pembrolizumab represent a new Table 1. Checkpoint inhibitors class of immunotherapeutic drugs for treating patients with Drug class (trade name, manufacturer) advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response Anti-CTLA-4 to tumor antigens by inhibiting T-cell autoregulation. As a Ipilimumab (Yervoy, Bristol-Myers Squibb) consequence, they can be associated with immune-related adverse Tremelimumab (AstraZeneca, compassionate use only) events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective Anti-PD-1 clinical chart review, including serologic, hematology, and Nivolumab (Opdivo, Bristol-Myers Squibb) chemistry laboratory results, of two patients who developed Pembrolizumab (Keytruda, Merck Sharp & Dohme) red blood cell (RBC) autoantibodies during treatment with a Pidilizumab (Medivations, in clinical trials) checkpoint inhibitor. Serologic testing of blood samples from these patients during induction therapy with ipilimumab and Anti-PD-L1 nivolumab, respectively, showed their RBCs to be positive by Atezolizumab (Genentech, in clinical trials) the direct antiglobulin test (IgG+, C3+) and their plasma to Durvalumab (AstraZeneca, approved bladder cancer) contain panreactive RBC autoantibodies. Neither patient had evidence of hemolysis. Both patients developed an additional CTLA-4 = cytotoxic T-lymphocyte–associated antigen 4; PD-1 = programmed cell death protein 1; PD-L1 = programmed cell death ligand 1.
    [Show full text]
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [Show full text]
  • Immune Checkpoint Inhibition in DLBCL Immunotherapy: “The Cure Is Inside Us”
    Mariano Provencio Servicio de Oncología Médica Hospital Universitario Puerta de Hierro Immune checkpoint inhibition in DLBCL Immunotherapy: “The Cure is Inside Us” § Our immune system prevents or limit infections by foreign antigens expressed in microorganisms (bacteria, viruses, etc.) § Our immune system can also recognize and destroy cancer cells….. • However, cancer cells have developed “escape mechanisms” to avoid their destruction by immune cells…“put the brakes on” • Immuno-Oncology: Find ways of “unleashing” the power of our body’s immune system to treat or prevent cancer…T-lymphocytes (T- cells) Detectives Dendritic cells Killer –T cells Microenvironment antigen (flags) Detectives Dendritic cells Killer –T cells Tumor infiltranting T cell recognizable ags Cor e Algorithms Margin Neo-antigens antigen (flags) 5 6 Scott DW et al. Nature Rev 2014 Strategy approach § Effective immune response: barriers § microenviroment § Activate anti-tumor immune response § inhibitory receptors: blocking antibodies § Nivo, Pembro, Ipi,…(anti PD 1) (CTLA4) § combining 2 checkpoint inhibitors § combining with chemotherapy § activate receptors: agonist § Urelumab § Utumilumab § Varlilumab Strategy approach § Effective immune response: barriers § microenviroment Inactivated effector T cell angiogenesis metabolism Strategy approach PDL-1 Effective immune CTLA-4 response: barriers Lymphoma PDL-1 PD-1 PDL-1 TIM-3 PDL-1 PDL-1 mTOR LAG-3 OXPHOS MHC1 Aerobic glycolysis Interferon gamma EB virus T cell activation antigen presenting cells Strategy approach §
    [Show full text]
  • Immune-Checkpoint Blockade Therapy in Lymphoma
    International Journal of Molecular Sciences Review Immune-Checkpoint Blockade Therapy in Lymphoma Ayumi Kuzume 1,2, SungGi Chi 1 , Nobuhiko Yamauchi 1 and Yosuke Minami 1,* 1 Department of Hematology, National Cancer Center Hospital East, Kashiwa 277–8577, Japan; [email protected] (A.K.); [email protected] (S.C.); [email protected] (N.Y.) 2 Department of Hematology, Kameda Medical Center, Kamogawa 296–8602, Japan * Correspondence: [email protected]; Tel.: +81-4-7133-1111; Fax: +81-7133-6502 Received: 11 June 2020; Accepted: 28 July 2020; Published: 30 July 2020 Abstract: Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with malignant lymphoma and their efficacy has been reported. For example, in Hodgkin lymphoma, immune-checkpoint blockade has resulted in response rates of 65% to 75%. However, in non-Hodgkin lymphoma, the response rate to immune-checkpoint blockade was lower. In this review, we evaluate the biology of immune-checkpoint inhibition and the current data on its efficacy in malignant lymphoma, and identify the cases in which the treatment was more effective.
    [Show full text]
  • On the Horizon: Immuno-Oncology (I-O) Combinations
    Immuno-Oncology (I-O) Combinations • Jeffrey A. Sosman, MD • Robert H. Lurie Comprehensive Cancer Center of Northwestern University The Cancer–Immunity Cycle Daniel Chen and Ira Mellman Immunity, Volume 39, Issue 1, 2013, 1 - 10 The Cancer–Immunity Cycle Daniel Chen and Ira Mellman Immunity, Volume 39, Issue 1, 2013, 1 - 10 Stimulatory and Inhibitory Factors in the Cancer-Immunity Cycle Each step of the Cancer-Immunity Cycle requires the coordination of numerous factors, both stimulatory and inhibitory in nature. Stimulatory factors shown in green promote immunity, ... Where will Improvements come from? • Combinations: – Based on Template: anti-PD-1/PD-L1 or with anti-PD- 1/anti-CTLA-4 • Block other co-inhibitory: LAG3, TIM3, KIR, VISTA • Activate co-stimulatory: 4-1BB, OX-40, GITR, CD27, ICOS • Block inhibitory molecules- IDOi, TGFbi, CSF1Ri, anti-IL-6 or anti- IL-10 • Effect trafficking- anti-VEGF, CCL5, CXCR4i • Vaccines- TVEC- oncolytic virus, Neoantigen, other cellular • Adoptive Cellular therapy- TIL, CAR-T cells, TCR T-cells Where will Improvements come from? • Combinations: – Based on Template: anti-PD-1/PD-L1 or with anti-PD- 1/anti-CTLA-4 • Signal Inhibition, BRAF directed (BRAFi+MEKi), MEKi, PI3K inhibition (PTEN effects) • Cytokines- IL-2, IFN a,b,g,, Directed cytokines (FAP-IL-2v or CEA-IL-2v) • Epigenetic modulation- gene expression and EVR expression • Microbiome modification- fecal transplants • Chemotherapy other cytotoxics • Localized Irradiation SBRT, SRS T cells in Tumors Express Multiple Immunoinhibitory Receptors
    [Show full text]
  • 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
    [Show full text]
  • Genomics Enhances Clinical Immuno-Oncology Trials
    Genomics enhances Clinical Immuno-oncology Trials Patrice Hugo, Ph.D. Chief Scientific Officer Personalized Medicine World Congress, Mountain View, January 26, 2016 COMPANY CONFIDENTIAL Copyright ©2015 Q2 Solutions. All rights reserved. Introducing Q2 Solutions, a Quintiles-Quest Joint Venture Established 02 Jul 2015 Consulting Real World and Late Phase Diagnostic Testing Drug Screening Portfolio & Strategy Planning Technology Solutions Diagnostic Products Informatics Clinical Trial Execution Patient and Provider Healthcare IT Engagement Wellness and Risk Management LaboratoriesLaboratories Product Marketing and Sales Employer Health ClinicalClinical Trials Trials Central Labs Central Labs Anatomic Pathology Anatomic Pathology (CT) BioAnalytical (Advion) Vaccine Testing (Focus Diagnostics Clinical Trials) Genomics (EA) Biorepository COMPANY CONFIDENTIAL 2 Q2 Solutions Footprint & Scientific Distribution Edinburgh Oss Indianapolis Beijing Teterboro Valencia Ithaca Tokyo Mumbai SJC EA Atlanta Singapore Pretoria Central Lab Hubs Supporting more than 180,000 AP labs investigative sites worldwide Molecular testing/Genetics Assay Development ADME-BioA-Immunogenicity COMPANY CONFIDENTIAL 3 The Opportunity: Immuno-oncology As The Future Of Cancer Treatment • Over 45 immuno-oncology drugs approved (US)* • 57 immuno-oncology drugs in development* • Over 250 studies registered/ongoing* • Increasing number of relevant publications annually** Brahmer et al, N Engl J Med 2015; 373:123-135 COMPANY CONFIDENTIAL 4 Expansion of PD-1/PL-L1 drugs into multiple
    [Show full text]
  • The Two Tontti Tudiul Lui Hi Ha Unit
    THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int .
    [Show full text]
  • WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A01N 43/00 (2006.01) A61K 31/33 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/US2016/028383 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 20 April 2016 (20.04.2016) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/154,426 29 April 2015 (29.04.2015) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: KARDIATONOS, INC. [US/US]; 4909 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Lapeer Road, Metamora, Michigan 48455 (US).
    [Show full text]
  • Ep 3178848 A1
    (19) TZZ¥__T (11) EP 3 178 848 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 14.06.2017 Bulletin 2017/24 C07K 16/28 (2006.01) A61K 39/395 (2006.01) C07K 16/30 (2006.01) (21) Application number: 15198715.3 (22) Date of filing: 09.12.2015 (84) Designated Contracting States: (72) Inventor: The designation of the inventor has not AL AT BE BG CH CY CZ DE DK EE ES FI FR GB yet been filed GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (74) Representative: Cueni, Leah Noëmi et al Designated Extension States: F. Hoffmann-La Roche AG BA ME Patent Department Designated Validation States: Grenzacherstrasse 124 MA MD 4070 Basel (CH) (71) Applicant: F. Hoffmann-La Roche AG 4070 Basel (CH) (54) TYPE II ANTI-CD20 ANTIBODY FOR REDUCING FORMATION OF ANTI-DRUG ANTIBODIES (57) The present invention relates to methods of treating a disease, and methods for reduction of the formation of anti-drug antibodies (ADAs) in response to the administration of a therapeutic agent comprising administration of a Type II anti-CD20 antibody, e.g. obinutuzumab, to the subject prior to administration of the therapeutic agent. EP 3 178 848 A1 Printed by Jouve, 75001 PARIS (FR) EP 3 178 848 A1 Description Field of the Invention 5 [0001] The present invention relates to methods of treating a disease, and methods for reduction of the formation of anti-drug antibodies (ADAs) in response to the administration of a therapeutic agent.
    [Show full text]
  • PD-L1 Expression Correlated with P53 Expression in Pediatric Glioblastoma Multiforme
    brain sciences Article PD-L1 Expression Correlated with p53 Expression in Pediatric Glioblastoma Multiforme Jakub Litak 1 , Wiesława Grajkowska 2, Justyna Szumiło 3, Paweł Krukow 4 , Ryszard Maciejewski 5 , Jacek Roli ´nski 1,* and Cezary Grochowski 6,* 1 Department of Immunology, Medical University of Lublin, Chod´zki4a, 20-093 Lublin, Poland; [email protected] 2 Department of Pathology, The Children’s Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland; [email protected] 3 Chair and Department of Clinical Pathomorphology, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] 4 Department of Clinical Neuropsychiatry, Medical University of Lublin, 20-439 Lublin, Poland; [email protected] 5 Department of Anatomy, Medical University of Lublin, 20-400 Lublin, Poland; [email protected] 6 Laboratory of Virtual Man, Chair of Anatomy, Medical University of Lublin, 20-093 Lublin, Poland * Correspondence: [email protected] (J.R.); [email protected] (C.G.) Abstract: High-grade gliomas are infrequent in the pediatric population compared to adults, nev- ertheless, mortality and morbidity caused by malignant gliomas in this group of patients remain significant. PD-L1 and PD-1 Immune checkpoints (IC) molecules maintain immunological balance between activation and suppression. Eighteen patients with a histopathological diagnosis of pediatric glioblastoma multiforme (GBM, WHO IV) were studied. In total, PD-L1 expression was detected Citation: Litak, J.; Grajkowska, W.; in 8 patients (44%). The molecular aspect of IC and immunotherapy targeted on PD-1/PD-L1 axis Szumiło, J.; Krukow, P.; Maciejewski, R.; Roli´nski,J.; Grochowski, C. PD-L1 in pediatric population may be a promising adjuvant therapy in pediatric glioblastoma multiform Expression Correlated with p53 treatment, however, this subject requires further investigation.
    [Show full text]