AstraZeneca showcases breadth of Oncology portfolio at AACR 2016 Annual Meeting

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
first-in-class potent and selective inhibitor of Ataxia telangiectasia mutated (ATM) kinase

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
Clinical Trials Plenary Session 2

Early Clinical Trials of Agents Targeting DNA or the Epigenome

Sunday 17 Apr 16:15-18:15
Room 291, Morial Convention Center

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
Clinical Trials Plenary Session 2

Early Clinical Trials of Agents Targeting DNA or the Epigenome
Sunday 17 Apr 16:15-18:15
Room 291, Morial Convention Center

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
Convention Center, Halls G-J, Poster Section 14

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
Convention Center, Halls G-J, Poster Section 18

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
Convention Center, Halls G-J, Poster Section 14

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
Convention Center, Halls G-J, Poster Section 24

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
Experimental and Molecular Therapeutics

Novel Antitumour DNA-Reactive Agents
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 15

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
Molecular and Cellular Biology/Genetics

Cell Death 3
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 4

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
Convention Center, Halls G-J, Poster Section 21

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
Immunology

Session Title TBD
Monday 18 Apr 15:00-17:00
New Orleans Theater B, Morial Convention Center

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
Immunology

Potentiating Immunotherapy Responses with Generation Agents and Combinatorial Partners

Tuesday 19 Apr 15:00-17:00
New Orleans Theater B, Morial Convention Center

Abstract #4361

Stewart R

Generation and Characterisation of MEDI1873 A Novel Hexameric GITRL Fusion Protein and Potent Agonist of the GITR Receptor

Poster
Immunology

Immune Modulating Agents 1

Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 26

Poster Board #22, Abstract #561

Mullins S

Local immune activation resulting in tumor growth inhibition with MEDI9197 - an intratumorally administered TLR7/8 agonist

Poster
Immunology

Immune Modulation Agents and Therapeutic Antibodies

Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 25

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
Immunology

Immune Microenvironment and Antitumor Immunity

Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 24

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
Convention Center, Halls G-J, Poster Section 10

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
Immunology

Immune Checkpoints 1

Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 26

Poster Board #26, Abstract #2342

Odate S

Inhibition of STAT3 with oligonucleotide antisense molecule, AZD9150 increases the chemosensitivity and decreases tumorigenicity of neuroblastoma

Poster
Tumor Biology

Pediatric Cancer Molecular Pathways

Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 31

Poster Board #2, Abstract #2439

Harper J

Exploring the oncolytic potential of Newcastle Disease virus

Poster
Clinical Research

Adoptive Cell Therapy, Immune Checkpoints, and Vaccines

Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 21

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
Tumor Biology

Immunomodulation and Immunotherapy

Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 31

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
Immunology

Immune Response Monitoring: Preclinical

Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 23

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
Immunology

Immune Modulation Agents 2

Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 22

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
Experimental and Molecular Therapeutics

Novel Antitumor Agents
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 17

Poster Board #6, Abstract #325

Avivar-Valderas A

Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer

Poster
Experimental and Molecular Therapeutics

Cellular Processes and Responses to Therapy
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 14

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
Experimental and Molecular Therapeutics

PI3K/AKT Inhibitors
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 19

Poster Board #20, Abstract #389

Feng S

AZD4547 and AZD5363 synergistically inhibit prostate cancer progression by modulating MAPK and AKT activation

Poster
Molecular and Cellular Biology/Genetics

Oncogenes and Tumor Suppressor Genes and Pathways
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 9

Poster Board #24, Abstract #1174

Barry E

Targeting MET Exon 14 mutations with the selective small molecule inhibitor Savolitinib

Poster
Molecular and Cellular Biology/Genetics

Oncogene Function, Regulation and Targeting
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 8

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 and Molecular Therapeutics

Experimental Therapeutics
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 16

Poster Board #8, Abstract #2087

Rodrik-Outmezguine VS

Overcoming mTOR Resistance Mutations with a new generation mTOR inhibitor

Poster
Experimental and Molecular Therapeutics

New Drugs, Therapeutic Targets, and Treatment Approaches
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 18

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
Session Category TBD

Late-Breaking Research: Experimental and Molecular Therapeutics 2
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 12

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
Experimental and Molecular Therapeutics

Preclinical Radiotherapeutics
Tuesday 19 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 18

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
Clinical Research

Molecular Classification and Genomic Applications
Tuesday 19 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 23

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
Molecular and Cellular Biology/Genetics

Cell Death 1

Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 2

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
Experimental and Molecular Therapeutics

Targeting Protein Kinases, Death Pathways, and the Tumor Microenvironment

Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 19

Poster Board #26, Abstract #3864

Deng J

Pre-clinical study using KRAS mutant mouse models for lung cancer immunotherapy

Poster
Tumor Biology

Mechanisms of Tumorigenesis in Animal Models of Cancer 2
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 32

Poster Board #22, Abstract #4184

McEachern K

Predicting response to Mcl-1 targeting agents in NSCLC and Multiple Myeloma

Poster
Molecular and Cellular Biology/Genetics

Cell Death 3
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 4

Poster Board #8, Abstract #3558

Palakurthi S

Utilizing NSCLC PDXs derived from patients on osimertinib (AZD9291) clinical trials to further refine therapeutic strategies

Poster
Tumor Biology

Therapeutic Studies in Patient-derived Xenografts
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 33

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
Experimental and Molecular Therapeutics

Combination Therapies and Approaches to Sensitizing Cancer Cells to Drugs
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 15

Poster Board #3, Abstract #4662

Chen H

Therapeutic activity of bivalent BRD4 inhibitor AZD5153 in haematological cancers

Poster
Experimental and Molecular Therapeutics

Epigenetic Agents
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 16

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
Experimental and Molecular Therapeutics

Monoclonal Antibodies and Antibody-Drug Conjugates
Tuesday 19 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 15

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.

CONTACTS

Media Enquiries

Neil Burrows UK/Global +44 20 7604 8032
Vanessa Rhodes UK/Global +44 20 7604 8037
Karen Birmingham UK/Global +44 20 7604 8120
Jacob Lund Sweden +46 8 553 260 20
Michele Meixell US +1 302 885 2677


Investor Enquiries

UK

Thomas Kudsk Larsen   +44 7818 524185
Eugenia Litz RIA +44 7884 735627
Nick Stone CVMD +44 7717 618834
Craig Marks Finance +44 7881 615764
Christer Gruvris Consensus Forecasts +44 7827 836825


US

Lindsey Trickett Oncology, ING +1 240 543 7970
Mitch Chan Oncology +1 240 477 3771
Dial / Toll-Free   +1 866 381 7277

Key: RIA - Respiratory, Inflammation and Autoimmunity, CVMD - Cardiovascular and Metabolic Disease, ING - Infection, Neuroscience and Gastrointestinal