A Year of Challenges, Opportunities and Hope. Vall D'hebron Institute of Oncology (VHIO) CELLEX CENTER C/Natzaret, 115 – 117 08035 Barcelona, Spain Tel

Total Page:16

File Type:pdf, Size:1020Kb

A Year of Challenges, Opportunities and Hope. Vall D'hebron Institute of Oncology (VHIO) CELLEX CENTER C/Natzaret, 115 – 117 08035 Barcelona, Spain Tel 2020SCIENTIFIC REPORT A year of challenges, opportunities and hope. Vall d'Hebron Institute of Oncology (VHIO) CELLEX CENTER C/Natzaret, 115 – 117 08035 Barcelona, Spain Tel. +34 93 254 34 50 www.vhio.net Direction: Amanda Wren Photography: Katherin Wermke Design: Parra estudio Vall d'Hebron Institute of Oncology (VHIO) | 2021 VALL D'HEBRON INSTITUTUE OF ONCOLOGY (VHIO) SCIENTIFIC REPORT 2020 A year of challenges, opportunities and hope. Extended version online: memorias.vhio.net/2020 PDF version: memorias.vhio.net/2020/SR-VHIO-2020.pdf INDEX INTRODUCING VHIO 06 Foreword by VHIO’s Director 18 José "Pepe" Baselga, MD, PhD: In Memoriam (1959-2021) A personal tribute by VHIO's Director, Josep Tabernero 22 VHIO in 2020: A year of challenges, opportunities and hope. 52 Scientific Productivity: research articles 53 Selection of some of the most relevant articles by VHIO researchers published in 2020 PRECLINICAL & TRANSLATIONAL RESEARCH 66 Cellular Plasticity & Cancer Group 68 Chromatin Dynamics in Cancer Group 70 Experimental Therapeutics Group 72 Gene Expression & Cancer Group 74 Growth Factors Group 76 Mouse Models of Cancer Therapies Group 78 Prostate Cancer Translational Research Group 80 Sarcoma Translational Research Group 82 Stem Cells & Cancer Group 84 Tumor Biomarkers Group 86 Tumor Immunology & Immunotherapy Group CLINICAL RESEARCH 90 Breast Cancer & Melanoma Group 92 Early Clinical Drug Development Group 94 Experimental Hematology Group 96 Gastrointestinal & Endocrine Tumors Group 98 Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group 100 Gynecological Malignancies Group 102 Hereditary Cancer Genetics Group 104 Oncology Data Science (ODysSey) Group 106 Radiation Oncology Group 108 Radiomics Group 110 Thoracic Tumors & Head and Neck Cancer Group CORE TECHNOLOGIES 114 Bioinformatics Support Unit 116 Cancer Genomics Group 118 Molecular Oncology Group 120 Proteomics Group INSTITUTIONAL PROGRAMS & TASK FORCES 122 Institutional Programs 126 VHIO’s Task Forces VHIO’s TRANSVERSAL CLINICAL TRIALS CORE SERVICES 130 Clinical Trials Office 133 Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch 136 Clinical Research Oncology Nurses 138 Clinical Research Oncology Pharmacy Unit 140 Molecular Prescreening Program 142 Quality & Processes Unit VHIO's SCIENTIFIC COORDINATION AREA 144 Scientific oordinationC Area 146 Academic CRO (VHIO – aCRO) 148 Full listing of articles published by VHIO Investigators in 2020 172 Funding, Consortia & Accreditation 182 New funding and projects in 2020 3 A year of challenges, opportunities and hope. Championed by VHIO’s Director, Josep Tabernero, our Principal Investigators as well as the Heads of our Transversal Clinical Trials Core Services, Units and Programs, spearhead efforts aimed at solving cancer sooner. They lead their respective groups and teams to turn obstacles in oncology into opportunities, and work tirelessly to resolve current and future challenges in combating this hugely complex disease. Throughout 2020, the COVID-19 pandemic wreaked its havoc at societal level, affecting all aspects of humanity everywhere. It has undoubtedly had a tremendous effect on how the cancer research community has had to re-think interaction, adapt infrastructures and approaches to ensure that progress against cancer advances, no matter how disruptive this past year has been. To mark this terribly challenging year, we invited each of our Group and Unit leaders to reflect on 2020, and submit a noun, adjective, concept, or priority area, which they felt was particularly relevant- though not exclusive- to this past year. 4 VHIO Scientific Report 2020 surmountable teamwork proactive dedication generosity restructure MARÍA ABAD JOAQUÍN ARRIBAS JUDITH BALMAÑA MARTA BELTRÁN FRANCESC BOSCH FRANCESC CANALS exacting transformation resolve digital support flexibility JOAN CARLES RODRIGO DIENSTMANN ENRIQUETA FELIP JOSÉ FERNÁNDEZ ELENA GARRALDA JORDI GIRALT reinvention zeal together growth ALENA GROS TERESA MACARULLA JOAQUIN MATEO SUSANA MUÑOZ determination creativity valor resilience hope PAOLO G. NUCIFORO ANA OAKNIN JOSEP TABERNERO HÉCTOR G. PALMER SANDRA PEIRÓ moving patients' opportunities fortitude safety fortified forward collegiality M ÁNGELES PEÑUELAS RAQUEL PEREZ-LOPEZ ALEX PIRIS MARÍA QUERALT GEMMA SALA CRISTINA SAURA innovation reflection connected adaptive zooming strength JOAN SEOANE VIOLETA SERRA CÉSAR SERRANO LAURA SOUCEK JOSEP VILLANUEVA ANA VIVANCOS INTRODUCING VHIO FOREWORD leaders to reflect on 2020, and come up with a noun, adjective, concept, or priority area, which they each considered as particularly relevant -- though not exclusive -- to this momentous past year. Written on each of their respective masks (see fold-out pages 4-5), the design depicts the very familiar Zoom virtual meeting scenario, which is so symbolic of the COVID-19 era. Due to the safety and logistical considerations brought about Josep Tabernero by COVID-19, and to reflect Director, Vall d’Hebron Institute of Oncology (VHIO) the reality of balancing those physically working in the lab and clinical settings with those working from home, we 2020: An Extraordinary revisited our approach to this year’s report’s photo shoot. We Year for Biomedicine, translated this obstacle into Cancer Science and opportunity. With the exception of our larger groups, we sought to include Clinical Oncology as many group members as possible without masks. Each photo was taken individually, Considering the many challenges vaccines against related viruses; at a distance, in locations away posed by the COVID-19 years of critical basic research from areas dedicated to the pandemic in 2020, I cannot in understanding and applying care of our cancer patients. We forget the particularly dark times. RNA biology; faster ways to also welcomed faculty who were How this terrible virus swept the manufacture vaccines; hefty working at home during each world and ravaged human lives, funding that enabled the running photo session, inviting them to with a devastating death toll. But, of multiple trials in parallel; and send their photos from home. in the context of biomedicine, regulatory bodies moving more there were many bright moments quickly in response. COVID-19: from crisis that translated into opportunities to opportunity and hope. There are many lessons here that could be applied to other Using a combination of surveys This pandemic has shone a diseases including cancer in and interviews of oncology light on the breathtaking ability order to accelerate progress clinical investigators globally, of medical science to identify and accelerate improved clinical and analyses of data from IQVIA and combat a major new threat outcomes for countless patients and Clinical Trials.gov, a study(1) to public health globally. At worldwide. explored how COVID-19 has lightning speed, researchers Shaped by these reflections, affected the management of around the world worked ongoing clinical trials. tirelessly together to successfully the theme of this year’s report develop COVID-19 vaccines. -- VHIO in 2020: a year of The focus of this research was challenges, opportunities and to provide an initial evaluation Open They were able to do so quickly hope -- captures our experiences, of COVID-19 on the landscape for several reasons: research endeavors, and collective spirit. of clinical trials for cancer experience in developing We invited our Group and Unit around the world. As noted 6 VHIO Scientific Report 2020 A year of challenges, opportunities and hope. by the authors, while the data extensive changes to reduce institutions in treating cancer were limited by sample size, the COVID-19 exposure among during such difficult times. findings indicated that patient patients and our healthcare enrolment in active clinical trials teams. In addition to some We also co-led a multi-center (4) for cancer has been severely deviations from existing observational study to hampered by the pandemic protocols and administration provide a clinical portrait of the during the survey assessment of novel therapies, including epidemic in European cancer period (23 March–3 April). immunosuppressive treatment patients .This study addressed regimens, we also adopted several important questions Crucially, their data highlighted the technology-based as well as as to whether, within a broader importance of getting telemedicine remote interventions and patient population of cancer patients, running smoothly in advance to care activities to reduce on-site outcome of COVID-19 is more enable a seamless transition in monitoring visits and in-person strongly related to patients’ patient care. I completely agree. visits, thereby minimizing risk of demographic factors including The application of telemedicine viral infection and disease spread. age and comorbidities over has most certainly been oncologic features. expedited by COVID-19, possibly Regarding the future impact of representing a tipping point, the COVID-19 on cancer treatment Between February and April advent of remote patient care in and research, we should expect 2020, almost 900 patients with bringing crucial medical expertise further challenges ahead, confirmed COVID-19 and cancer to more patients. especially given the threat of were identified across the 19 new waves and strains. We surveyed European centers. (This Authors of a comprehensive must all continue to adapt was, at the time, the largest and (2) survey on what physicians have and respond to the ongoing most geographically diverse study learned and
Recommended publications
  • Polatuzumab Vedotin - R/R DLBCL RG7769 PD1-TIM3 Bimab - Solid Tumors NSCLC RG7446 Tecentriq – Her2-Pos
    Pipeline summary Marketed products additional indications Global Development late-stage trials pRED (Roche Pharma Research & Early Development) gRED (Genentech Research & Early Development) 1 Changes to the development pipeline FY 2018 update New to phase I New to phase II New to phase III New to registration 3 NMEs: 2 NMEs transitioned from Ph1 1 NME transitioned from Ph2: 2 NMEs + 1 AI transitioned from Ph2 RG6217 - HBV RG7906 - psychiatric disorders RG6042 HTT ASO - Huntington’s following filing in EU and US: RG6237 - neuromuscular disorders RG6058 tiragolumab + Tecentriq - 6 AIs: RG7596 polatuzumab vedotin - r/r DLBCL RG7769 PD1-TIM3 biMAb - solid tumors NSCLC RG7446 Tecentriq – Her2-pos. BC neoadj RG6268 entrectinib - NSCLC ROS1+ 1 AI: 1 NME starting Ph2 RG7446 Tecentriq – high risk NMIBC RG6268 entrectinib – NTRK1 pan-tumor RG7601 Venclexta + gilteritinib – r/r RG6180 iNeST (personalized cancer RG6152 Xofluza - influenza hosp. patients 3 AIs transitioned from Ph3 following AML vaccine) + pembrolizumab - malignant RG6152 Xofluza – influenza pediatric filing in EU and US: melanoma patients RG7446 Tecentriq + nab-paclitaxel 1L 1 NME following termination of Ph3 RG7601 Venclexta - r/r MM t(11:14) non sq NSCLC RG7412 crenezumab – familial RG7601 Venclexta + HMA/LDAC - 1L RG7446 Tecentriq + nab-paclitaxel Alzheimer’s disease healthy individuals AML* 1LTNBC RG7446 Tecentriq + chemo - 1L extensive 1 AI: stage SCLC RG7446 Tecentriq SC – NSCLC Removed from phase I Removed from phase II Removed from phase III Removed from registration 2 NMEs:
    [Show full text]
  • Scientific Annual Report 2019
    Scientific Annual Report 2019 Scientific Annual Report 2019 Contents 2 Introduction 14 Board members Director of Research 18 Group leaders 18 Neil Aaronson 37 Kees Jalink 56 Hein te Riele 19 Reuven Agami 38 Jos Jonkers 57 Lonneke van de Poll 20 Leila Akkari 39 Marleen Kok 58 Winette van der Graaf 21 Regina Beets-Tan 40 Pia Kvistborg and Olga Husson 22 Roderick Beijersbergen 41 Tineke Lenstra 60 Uulke van der Heide 23 Jos Beijnen 42 Sabine Linn 61 Michiel van der Heijden 24 André Bergman 43 René Medema 62 Wim van Harten 25 René Bernards 44 Gerrit Meijer and 63 Flora van Leeuwen and 26 Christian Blank Remond Fijneman Matti Rookus 27 Eveline Bleiker 46 Daniel Peeper 65 Fred van Leeuwen 28 Gerben Borst 47 Anastassis Perrakis 66 Maarten van Lohuizen 29 Thijn Brummelkamp 48 Benjamin Rowland 67 Jacco van Rheenen 30 Karin de Visser 49 Sanne Schagen 68 Bas van Steensel 31 Elzo de Wit 50 Alfred Schinkel 69 Olaf van Tellingen 32 William Faller 51 Marjanka Schmidt 70 Emile Voest 33 John Haanen 52 Ton Schumacher 71 Jelle Wesseling 34 Hugo Horlings 53 Titia Sixma 72 Lodewyk Wessels 35 Heinz Jacobs 54 Jan-Jakob Sonke 73 Lotje Zuur 36 Jacqueline Jacobs 55 Arnoud Sonnenberg 74 Wilbert Zwart 78 Division of 84 Division of 90 Division of Diagnostic Oncology Medical Oncology Surgical Oncology 96 Division of 102 Division of 110 Technology Radiation Oncology Pharmacology Transfer Office and Biometrics 112 Research Facilities 126 Education in 134 Clinical Oncology trials 164 Invited 166 Research 194 Personnel speakers projects index Netherlands Cancer Institute Plesmanlaan 121 1066 CX Amsterdam The Netherlands www.nki.nl Scientific Annual Report 2019 Introduction It is my pleasure to present the 2019 Scientific Annual Report of the Netherlands Cancer Institute.
    [Show full text]
  • 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]
  • Roche/Genentech Managed RG7986 ADC R/R NHL CHU Chugai Managed IONIS IONIS Managed 74 Status As of January 28, 2016 PRO Proximagen Managed
    Roche 2015 results London, 28 January 2016 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche’s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website www.roche.com All mentioned trademarks are legally protected.
    [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]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • Roche Template
    Changes to the development pipeline Q3 2020 update New to phase I New to phase II New to phase III New to registration 7 NMEs: 2 NMEs: 4 NMEs: 1 NME: RG6091 UBE3A LNA - Angelman syndrome RG7992 FGFR1 x KLB - NASH RG6107 crovalimab - PNH RG6396 Gavreto (pralsetinib) - RET fusion- RG6286 NME - colorectal cancer CHU Oncolytic Type 5 adenovirus - esophageal RG6413+RG6412 REGN-COV2 - SARS-CoV-2 positive NSCLC RG6315 NME - systemic sclerosis cancer prophylaxis RG6330 KRAS G12C - KRAS-mutant solid tumors RG6171 SERD(3) ER+/HER2 - metastatic breast 2 AIs: RG6418 NLRP3 inhibitor - inflammation 5 AIs: cancer RG3648 Xolair - asthma home use 4D-MT 4D-R125 - X-linked retinitis pigmentosa RG6171 SERD(3) - neoadjuvant HR+ breast 7 AIs: RG6396 Gavreto (pralsetinitb) - RET-mutant CHU CD137 agonist switch antibody - solid tumors cancer RG6058 tiragolumab+Tecentriq - stage III medullary thyroid cancer (MTC) RG6413+RG6412 REGN-COV2 - COVID-19+ unresectable 1L NSCLC 2 AIs: adult – ambulatory RG6058 tiragolumab+Tecentriq - locally adv RG7440 ipatasertib+Tecentriq - prostate cancer RG6413+RG6412 REGN-COV2 - COVID-19+ esophageal cancer previously treated with androgen receptor-targeted adult – hospitalized RG6321 PDS with ranibizumab - diabetic therapy retinopathy RG7446 Tecentriq+Venclexta - maintenance 1L RG7159 Gazyva - lupus nephritis ES-SCLC RG7601 Venclexta - 1L MDS RG7446 Tecentriq+cabozantinib - adv RCC RG7446 Tecentriq+cabozantinib - 2L NSCLC Removed from phase I Removed from phase II Removed from phase III Approvals 2 NMEs: 2 AIs: 3 AIs: 3 NMEs approved
    [Show full text]
  • The Angiopoietin-2 and TIE Pathway As a Therapeutic Target for Enhancing Antiangiogenic Therapy and Immunotherapy in Patients with Advanced Cancer
    International Journal of Molecular Sciences Review The Angiopoietin-2 and TIE Pathway as a Therapeutic Target for Enhancing Antiangiogenic Therapy and Immunotherapy in Patients with Advanced Cancer Alessandra Leong and Minah Kim * Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; afl[email protected] * Correspondence: [email protected] Received: 26 September 2020; Accepted: 13 November 2020; Published: 18 November 2020 Abstract: Despite significant advances made in cancer treatment, the development of therapeutic resistance to anticancer drugs represents a major clinical problem that limits treatment efficacy for cancer patients. Herein, we focus on the response and resistance to current antiangiogenic drugs and immunotherapies and describe potential strategies for improved treatment outcomes. Antiangiogenic treatments that mainly target vascular endothelial growth factor (VEGF) signaling have shown efficacy in many types of cancer. However, drug resistance, characterized by disease recurrence, has limited therapeutic success and thus increased our urgency to better understand the mechanism of resistance to inhibitors of VEGF signaling. Moreover, cancer immunotherapies including immune checkpoint inhibitors (ICIs), which stimulate antitumor immunity, have also demonstrated a remarkable clinical benefit in the treatment of many aggressive malignancies. Nevertheless, the emergence of resistance to immunotherapies associated with an immunosuppressive tumor microenvironment has restricted therapeutic response, necessitating the development of better therapeutic strategies to increase treatment efficacy in patients. Angiopoietin-2 (ANG2), which binds to the receptor tyrosine kinase TIE2 in endothelial cells, is a cooperative driver of angiogenesis and vascular destabilization along with VEGF. It has been suggested in multiple preclinical studies that ANG2-mediated vascular changes contribute to the development and persistence of resistance to anti-VEGF therapy.
    [Show full text]
  • PD-1 / PD-L1 Combination Therapies
    PD-1 / PD-L1 Combination Therapies Jacob Plieth & Edwin Elmhirst – May 2017 Foreword Sprinkling the immuno-oncology dust When in November 2015 EP Vantage published its first immuno- oncology analysis we identified 215 studies of anti-PD-1/PD-L1 projects combined with other approaches, and called this an important industry theme. It is a measure of how central combos have become that today, barely 18 months on, that total has been blown out of the water. No fewer than 765 studies involving combinations of PD-1 or PD-L1 assets are now listed on the Clinicaltrials.gov registry. This dazzling array owes much to the transformational nature of the data seen with the first wave of anti-PD-1/PD-L1 MAbs. It also indicates how central combinations will be in extending immuno-oncology beyond just a handful of cancers, and beyond certain patient subgroups. But the combo effort is as much about extending the reach of currently available drugs like Keytruda, Opdivo and Tecentriq as it is about making novel approaches viable by combining them with PD-1/PD-L1. On a standalone basis several of the industry’s novel oncology projects have underwhelmed. As data are generated it will therefore be vital for investors to tease out the effect of combinations beyond that of monotherapy, and it is doubtful whether the sprinkling of magic immuno-oncology dust will come to the rescue of substandard products. This is not stopping many companies, as the hundreds of combination studies identified here show. This report aims to quantify how many trials are ongoing with which assets and in which cancer indications, as well as suggesting reasons why some of the most popular approaches are being pursued.
    [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]
  • First-In-Human Phase I Study of Single-Agent Vanucizumab, a First-In
    Author Manuscript Published OnlineFirst on December 7, 2017; DOI: 10.1158/1078-0432.CCR-17-1588 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Hidalgo et al. Clin Cancer Res submission 2017 First-in-human phase I study of single-agent vanucizumab, a first-in- class bi-specific anti-angiopoietin-2/anti-VEGF antibody, in adult patients with advanced solid tumors Manuel Hidalgo1,2*; Maria Martinez Garcia3*; Christophe Le Tourneau4; Christophe Massard5; Elena Garralda2; Valentina Boni2; Alvaro Taus3; Joan Albanell3; Marie-Paule Sablin4; Marie Alt4; Ratislav Bahleda5; Andrea Varga5; Christophe Boetsch6; Izolda Franjkovic7; Florian Heil7; Angelika Lahr7; Katharina Lechner7; Anthony Morel6; Tapan Nayak6; Simona Rossomanno6; Kevin Smart8; Kay Stubenrauch7; Oliver Krieter7. *Joint first authors 1Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. 2START Madrid-CIOCC, HM Sanchinarro.3Medical Oncology Department, Hospital del Mar. Barcelona, Spain.4Department of Medical Oncology, Institut Curie, Saint-Cloud & Paris.5Department of Drug Development, Gustave Roussy, Villejuif, France.6Roche Innovation Center Basel, Basel, Switzerland.7Roche Innovation Center Munich, Penzberg, Germany.8Roche Innovation Centre Welwyn, Welwyn Garden City, United Kingdom. Running title: Phase I study of vanucizumab Keywords: Vanucizumab, RG7221, RO5520985, VEGF-A, Ang-2 Corresponding authors: 1 Downloaded from clincancerres.aacrjournals.org on September 27, 2021. © 2017 American Association for Cancer Research. Author Manuscript Published OnlineFirst on December 7, 2017; DOI: 10.1158/1078-0432.CCR-17-1588 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Hidalgo et al. Clin Cancer Res submission 2017 Manuel Hidalgo, Chief, Division Hematology Oncology, Director, Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Member of the Faculty of Medicine, Harvard Medical School, 330 Brookline Avenue - KS207, Boston, MA 02215, USA.
    [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]