More than 60 presentations featuring 26 potential medicines across four key scientific platforms, including DNA Damage Response (DDR) and Immuno-Oncology (IO)
14 April 2016
AstraZeneca and its global biologics research and development arm, MedImmune, will present 57 abstracts, deliver five oral presentations and two lectures as well as participating in a round-table session on PD-L1 diagnostic harmonisation at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans this week.
DNA Damage Response: an industry-leading portfolio
Three oral presentations will provide insight into AstraZeneca’s industry-leading DNA Damage Response (DDR) pipeline of potential medicines as both monotherapy and in combination:
- Phase I data evaluating the combination of first-in-class PARP inhibitor Lynparza (olaparib) and AKT inhibitor AZD5363 in germline BRCA and non-BRCA mutant advanced cancer patients (Abstract #CT1010)
- Early safety and efficacy data from a Phase Ib study of novel potential medicine AZD1775, a small molecule designed to inhibit the Wee1 kinase, which plays a critical role in the DNA damage repair that enables cell division (Abstract #CT013)
- Pre-clinical pharmacology of AZD0156, an ATM kinase inhibitor that detects DNA double strand breaks to enable downstream DNA repair and cell survival (Sunday 17 Apr - 14:15-16:15)
Andrew Mortlock, Vice President, Global Projects and Alliances, Oncology iMed at AstraZeneca said: “The data we will present at AACR underscore the scientific promise shown by our industry-leading DDR portfolio as well as the clinical potential of this pioneering approach to targeting tumour cells. With three new molecules now in the clinic and one on the market, we are following the science and exploring their potential in both monotherapy and in combination with other therapies.”
Immuno-Oncology: biomarkers, next-generation Immunotherapies, and combinations
AstraZeneca’s Immuno-Oncology research will feature prominently at AACR, including with new data from a comparative study of commonly used PD-L1 diagnostic tests in approximately 500 tumour biopsies (Abstract #LB-094; also included in the AACR media programme). AstraZeneca will also take part in a roundtable discussing the value of PD-L1 diagnostic testing - “The Blueprint Project: Harmonizing Companion Diagnostics across a Class of Targeted Therapies”, scheduled for Tuesday 19 April, 13.00 – 15.00 EST (Room 283, Morial Convention Center).
AstraZeneca will also provide updates on its exploration of biological targets beyond PD-L1 and CTLA-4, including MEDI1873, an agonist of the GITR receptor (Abstract #561) and MEDI9197, a TLR7/8 agonist (Abstract #1475), as well as the combination strategy of PD-L1/PD1 axis inhibition with several complementary mechanisms of action targeting NKG2A, OX40 and immTACs.
In addition, researchers at the congress will present the latest results from a Phase I/II trial of tremelimumab plus tumour ablation in patients with advanced hepatocellular carcinoma (HCC) (Abstract #2653).
David Berman, Senior Vice President, Head of Oncology Innovative Medicines, at MedImmune, said: “At AACR, we will present pre-clinical data and mechanistic characterisation that support our ongoing clinical trials exploring next-generation immuno-oncology targets and their combination with durvalumab. We will present a comparison of the different PD-L1 diagnostic assays to help advance the science for the field of PD1/L1 blockade. In addition, the activity of tremelimumab, a CTLA4 inhibitor, will be further evidenced.”
Tumour drivers and resistance: A key area of expertise
AstraZeneca will also present data on Tagrisso (osimertinib), exploring the utilisation of non-small cell lung cancer (NSCLC) xenograft models from patients on Tagrisso to refine therapeutic strategies (Abstract #5192). Tagrisso recently received accelerated approval as the first indicated treatment for patients with EGFR T790M mutation-positive metastatic NSCLC in the US, EU and Japan.
The company will also showcase its continued progress in therapies targeting the genetic drivers of cancer with breaking data on an early-stage mTOR inhibitor that has shown pre-clinical activity in prostate cancer. Specific posters include:
- Anti-tumour activity of mTOR inhibitor AZD2014 in a prostate cancer mouse model (Abstract #2147)
- Overcoming mTOR resistance mutations with a next-generation mTOR inhibitor (Abstract #389)
NOTES TO EDITORS
AstraZeneca/MedImmune key presentations at AACR
Lead author |
Abstract title |
Presentation details |
DNA Damage Response
Thomason AG |
Discovery and pre-clinical pharmacology of AZD0156: A |
Oral New Drugs on the Horizon Sunday 17 Apr 14:15-16:15 New Orleans Theater C, Morial Convention Center Webcast Available |
Bauer TM |
A Phase Ib, open-label, multi-center study to assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of AZD1775 monotherapy in patients with advanced solid tumors: Initial findings |
Oral Early Clinical Trials of Agents Targeting DNA or the Epigenome Sunday 17 Apr 16:15-18:15 Abstract #CT013 |
Michalarea V |
Phase I trial combining the PARP inhibitor Olaparib (Ola) and AKT inhibitor AZD5363 (AZD) in germline (g)BRCA and non-BRCA mutant (m) advanced cancer patients (pts) incorporating non-invasive monitoring of cancer mutations |
Oral Early Clinical Trials of Agents Targeting DNA or the Epigenome Abstract #CT010 |
Laing N |
Genetic analysis of tumors from a Phase II trial evaluating AZD1775, carboplatin and paclitaxel in patients with TP53-mutant ovarian cancer |
Poster Experimental and Molecular Therapeutics Novel Antitumor Agents Sunday 17 Apr 13:00–17:00 Poster Board #18, Abstract #337 |
Durant S |
Blood-brain barrier penetrating ATM inhibitor (AZ32) radiosensitises intracranial gliomas in mice |
Poster Experimental and Molecular Therapeutics Preclinical Radiotherapeutics Tuesday 19 Apr 08:00–12:00 Poster Board #1, Abstract #3041 |
Oplustil O’Connor L |
A camptothecin-containing nanoparticle-drug conjugate combination with DDR agents provides a novel approach to increasing therapeutic index |
Poster Experimental and Molecular Therapeutics Cell Death Pathways and DNA Repair Tuesday 19 Apr 13:00–17:00 Poster Board #19, Abstract #3721 |
Perez-Lopez R |
Diffusion-weighted imaging of bone metastases as treatment response biomarker in prostate cancer |
Poster Clinical Research Novel Molecular Diagnostics and Imaging Tuesday 19 Apr 13:00–17:00 Poster Board #3, Abstract #3973 |
Williams L |
Continuous, low intensity systemic dosing maximizes the therapeutic margin of Eg5/KSP inhibition in a model of urothelial cell carcinoma |
Poster Novel Antitumour DNA-Reactive Agents Poster Board #16, Abstract #3769 |
Cidado J |
AZ5576, a novel potent and selective CDK9 inhibitor, induces rapid cell death and achieves efficacy in multiple preclinical hematological models |
Poster Cell Death 3 Poster Board #22, Abstract #3572 |
Pike K |
Identifying high quality, potent and selective inhibitors of ATM kinase: Discovery of AZD0156 |
Poster Cancer Chemistry Drug Design Wednesday 20 Apr 08:00–12:00 Poster Board #24, Abstract #4859 |
Cuneo KC |
A dose escalation trial of the Wee1 inhibitor AZD1775, gemcitabine and concurrent radiation in locally advanced pancreatic cancer |
Poster Phase I Clinical Trials in Progress Monday 18 Apr 08:00–12:00 Convention Center, Halls G-J, Poster Section 13 Poster Board #16, Abstract #CT035 |
Min A |
Androgen receptor inhibitor enhances the anti-tumor effect of PARP inhibitor in breast cancer cells via modulation of DNA damage response |
Poster Late-Breaking Research: Experimental and Molecular Therapeutics 1 Monday 18 Apr 8:00 AM - 12:00 Convention Center, Halls G-J, Poster Section 11 Abstract #LB-107 |
Immuno-Oncology
Uppala A |
Tremelimumab plus tumor ablation for patients with hepatocellular carcinoma: Clinical results, Immunomonitoring analysis of peripheral T cells and tumor biopsies |
Oral Session Title TBD Abstract #2653 Press Programme |
Messenheimer DJ |
Timing of PD-1 blockade is critical to successful synergy with OX40 costimulation in preclinical mammary tumor models. |
Oral Potentiating Immunotherapy Responses with Generation Agents and Combinatorial Partners Tuesday 19 Apr 15:00-17:00 Abstract #4361 |
Stewart R |
Generation and Characterisation of MEDI1873 A Novel Hexameric GITRL Fusion Protein and Potent Agonist of the GITR Receptor |
Poster Immune Modulating Agents 1 Sunday 17 Apr 13:00-17:00 Poster Board #22, Abstract #561 |
Mullins S |
Local immune activation resulting in tumor growth inhibition with MEDI9197 - an intratumorally administered TLR7/8 agonist |
Poster Immune Modulation Agents and Therapeutic Antibodies Monday 18 Apr 08:00-12:00 Poster Board #6, Abstract #1475 |
Ghadially H |
Analysis of expression MHC class I chain-related gene A and B (MICA/B) in normal and tumour tissue |
Poster Immune Microenvironment and Antitumor Immunity Monday 18 Apr 08:00-12:00 Poster Board #12, Abstract #1451 |
Ratcliffe M |
A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative |
Poster Late-Breaking Research: Immunology Monday 18 Apr 08:00-12:00 Poster Board #18, Abstract #LB-094 |
Sola C |
NKG2A immune checkpoint blockade enhances the antitumor efficacy of PD1/PD-L1 inhibitors in a preclinical model |
Poster Immune Checkpoints 1 Monday 18 Apr 13:00-17:00 Poster Board #26, Abstract #2342 |
Odate S |
Inhibition of STAT3 with oligonucleotide antisense molecule, AZD9150 increases the chemosensitivity and decreases tumorigenicity of neuroblastoma |
Poster Pediatric Cancer Molecular Pathways Monday 18 Apr 13:00-17:00 Poster Board #2, Abstract #2439 |
Harper J |
Exploring the oncolytic potential of Newcastle Disease virus |
Poster Adoptive Cell Therapy, Immune Checkpoints, and Vaccines Monday 18 Apr 13:00-17:00 Poster Board #26, Abstract #2234 |
Jiang L |
PD-L1 expression and its relationship with other driver genes in non-small cell lung cancer (NSCLC |
Poster Immunomodulation and Immunotherapy Wednesday 20 Apr 08:00-12:00 Poster Board #26, Abstract #5140 |
Leyland R |
A Mouse GITRL Fusion Protein Drives T-Cell Activation and Antitumor Activity in Preclinical Mouse Models of Cancer |
Poster Immune Response Monitoring: Preclinical Wednesday 20 Apr 08:00-12:00 Poster Board #13, Abstract #4902 |
Bossi, G |
ImmTACs in combination with anti-CTLA-4 and anti-PD-L1 antibodies can re-direct the immune system more efficiently to eradicate cancer |
Poster Immune Modulation Agents 2 Wednesday 20 Apr 08:00-12:00 Poster Board #14, Abstract #4873 |
Huff CA |
Clinical cancer stem cell targeting in multiple myeloma: An early phase trial of the anti-CD19 monoclonal antibody, MEDI-551, in combination with lenalidomide and dexamethasone
|
Poster Phase II, III, and Special Population Clinical Trials Tuesday 19 Apr 13:00-17:00 Convention Center, Halls G-J, Poster Section 13 Poster Board #2, Abstract #CT102 |
Tumour Drivers & Resistance
Noble R |
Evaluating the consequences of MCT1 inhibition in Burkitt lymphoma following treatment with AZD3965 |
Poster Novel Antitumor Agents Poster Board #6, Abstract #325 |
Avivar-Valderas A |
Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer |
Poster Cellular Processes and Responses to Therapy Poster Board #6, Abstract #240 |
Sandi C |
Dual mTOR inhibitor, AZD2014, and castration induce immunogenic effects and anti-tumour activity in prostate cancer mouse model |
Poster PI3K/AKT Inhibitors Poster Board #20, Abstract #389 |
Feng S |
AZD4547 and AZD5363 synergistically inhibit prostate cancer progression by modulating MAPK and AKT activation |
Poster Oncogenes and Tumor Suppressor Genes and Pathways Poster Board #24, Abstract #1174 |
Barry E |
Targeting MET Exon 14 mutations with the selective small molecule inhibitor Savolitinib |
Poster Oncogene Function, Regulation and Targeting Poster Board #30, Abstract #1150 |
Diallo B |
The MEK1/2 inhibitor selumetinib appears as an efficient targeted therapy when used in an adjuvant setting in Patient-Derived Xenografts of Uveal Melanoma |
Poster Experimental Therapeutics Poster Board #8, Abstract #2087 |
Rodrik-Outmezguine VS |
Overcoming mTOR Resistance Mutations with a new generation mTOR inhibitor |
Poster New Drugs, Therapeutic Targets, and Treatment Approaches Poster Board #17, Abstract #2147 |
Yang Z |
Anti-tumor activities of AZD3759, a novel EGFR inhibitor with excellent penetration cross central nervous system (CNS), in pre-clinical animal models |
Poster Late-Breaking Research: Experimental and Molecular Therapeutics 2 Poster Board #24, Abstract #LB-217 |
Searle EJ |
Treatment with the novel Akt inhibitor AZD5363 following radiotherapy improves tumor control in mouse models of head and neck cancer |
Poster Preclinical Radiotherapeutics Poster Board #2, Abstract #3042 |
Greenawalt D |
Your targeted population might not be what you predict: Changes in tumor genetic landscapes post standard of care |
Poster Molecular Classification and Genomic Applications Poster Board #5, Abstract #3168 |
Greer Y |
MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor agonist, induces apoptotic cell death in breast cancer cells |
Poster Cell Death 1 Tuesday 19 Apr 13:00-17:00 Poster Board #4, Abstract #3494 |
De Velasco MA |
The Jak1/2 inhibitor AZD1480 suppresses tumor growth and metastasis in genetically engineered mouse models of PTEN-deficient prostate cancer |
Poster Targeting Protein Kinases, Death Pathways, and the Tumor Microenvironment Tuesday 19 Apr 13:00-17:00 Poster Board #26, Abstract #3864 |
Deng J |
Pre-clinical study using KRAS mutant mouse models for lung cancer immunotherapy |
Poster Mechanisms of Tumorigenesis in Animal Models of Cancer 2 Poster Board #22, Abstract #4184 |
McEachern K |
Predicting response to Mcl-1 targeting agents in NSCLC and Multiple Myeloma |
Poster Cell Death 3 Poster Board #8, Abstract #3558 |
Palakurthi S |
Utilizing NSCLC PDXs derived from patients on osimertinib (AZD9291) clinical trials to further refine therapeutic strategies |
Poster Therapeutic Studies in Patient-derived Xenografts Poster Board #18, Abstract #5192 |
Nilsson M |
Beta blockers abrogate EGFR TKI resistance induced by adrenergic receptor-mediated upregulation of IL-6 and modulation of the LKB1/AMPK/mTOR axis |
Poster Combination Therapies and Approaches to Sensitizing Cancer Cells to Drugs Poster Board #3, Abstract #4662 |
Chen H |
Therapeutic activity of bivalent BRD4 inhibitor AZD5153 in haematological cancers |
Poster Epigenetic Agents Poster Board #16, Abstract #4705 |
Capasso A |
A phase IB study of the combination of AZD6244 hydrogen sulfate (selumetinib) and cyclosporin A (CsA) in patients with advanced solid tumors with an expansion cohort in metastatic colorectal cancer |
Poster Phase I Clinical trials 2 Wednesday 20 Apr 08:00-12:00 Convention Center, Halls G-J, Poster Section 13 Abstract # CT146 |
Cortes J |
Phase I studies of AZD1208, a PIM kinase inhibitor, in patients with recurrent or refractory acute myelogenous leukemia or advanced solid tumors |
Poster Phase I Clinical Trials 2 Wednesday 20 Apr 08:00-12:00 Convention Center, Halls G-J, Poster Section 13 Poster Board #8, Abstract #CT147 |
Antibody Drug Conjugates
Li J |
MEDI4276, a HER2-targeting antibody tubulysin conjugate, displays potent in vitro and in vivo activity in preclinical studies |
Poster Monoclonal Antibodies and Antibody-Drug Conjugates Poster Board #16, Abstract #2970 |
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least 6 new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -- immuno-oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates -- and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology – as well as infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.
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Key: RIA - Respiratory, Inflammation and Autoimmunity, CVMD - Cardiovascular and Metabolic Disease, ING - Infection, Neuroscience and Gastrointestinal