AstraZeneca’s early and late-stage oncology portfolio showcased at AACR annual meeting and ELCC
New post-progression and quality of life data highlight Tagrisso and Imfinzi benefits in non-small cell lung cancer patients with high unmet need
Breadth and depth of DNA Damage Response portfolio reinforced, including overall survival data for Lynparza in metastatic breast cancer
Data for Tumour Drivers & Resistance and Immuno-Oncology agents demonstrate strength of next-generation pipeline
AstraZeneca and MedImmune, its global biologics research and development arm, will present updates from their early and late stage oncology pipelines at two major congresses this month. In total, 98 abstracts were accepted for the European Lung Cancer Conference (ELCC) in Geneva,11-14 April, and the American Association for Cancer Research (AACR) annual meeting in Chicago,14-18 April. The abstracts cover key data updates from the Phase III FLAURA and PACIFIC trials in non-small cell lung cancer (NSCLC), and the Phase III OlympiAD trial in BRCA-mutated metastatic breast cancer. They also highlight promising next-generation research from the company’s extensive pipeline in DNA damage response, Immuno-Oncology and Tumour Drivers & Resistance.
Dave Fredrickson, Executive Vice President, Head of Oncology Business Unit said: “Building on major regulatory approvals in the first quarter of 2018, AstraZeneca continues to deliver strong results from our innovative science and accelerated development programmes in oncology. At ELCC, we are sharing new data from two pivotal trials in lung cancer that will help inform treatment strategies for patients who, until now, have had very few options. At the AACR meeting, we will share pioneering early science across multiple tumour types.”
As part of the ‘Best of ELCC’ sessions, AstraZeneca will present post-progression outcomes from the FLAURA trial of Tagrisso versus the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib or gefitinib in 1st-line EGFR mutation-positive NSCLC (Abstract #128O). In addition, patient-reported outcomes data will also be presented from the FLAURA trial, showing improvements in key symptoms, supporting the potential use of Tagrisso in this setting (Abstract #139PD).
Patient-reported outcomes will be presented from the PACIFIC trial of Imfinzi in unresectable, Stage III NSCLC (Abstract #703), following its approval in the US for this indication.
AACR annual meeting
DNA Damage Response (DDR)
AstraZeneca will present data on its expanded portfolio of potential medicines which exploit DDR dependencies to selectively kill cancer cells across multiple tumour types. The first-in-class PARP inhibitor, Lynparza, will report final overall survival data from the pivotal OlympiAD trial in BRCA-mutated metastatic breast cancer (Abstract #CT038). Data exploring the clinical properties of Lynparza and four other PARP inhibitors will illustrate clinical efficacy and safety profiles (Abstract #LB-273/17).
New data will also be presented on AZD6738, an Ataxia Telangiectasia and Rad3-related (ATR) inhibitor (Abstracts #CT026/19, #LB-263/7 and #337/18) and AZD0156, a first-in-class inhibitor of Ataxia telangiectasia mutated (ATM) (Abstract #4909/5).
A series of presentations will share new insights into the science of Imfinzi, including IO-IO combination data from Study 006 (Abstract #CT113) and Study 10 (Abstract #CT113) in 2nd-line NSCLC patient populations.
Beyond Imfinzi, MedImmune will feature progress in its early IO pipeline, including the novel bispecific antibody MEDI5752, designed to target dual checkpoints on immune cells and leverage the synergistic potential of combined mechanisms in immunotherapy (Abstract #2776/9).
Tumour Drivers & Resistance
Data on AZD4573, a CDK9 inhibitor, will demonstrate rapid cell-death induction in haematological tumour models through depletion of MCL1 (Abstract #310/17). And early monotherapy and combination data on the novel ERK inhibitor AZD0364, (Abstract #1647/2) will show its effect on KRAS-mutated tumours when used in combination with MEK inhibitor, selumetinib (Abstract #1856/14).
AstraZeneca is presenting the results of the DREAM challenge, an open competition combining crowd-sourcing and the application of machine learning to generate new algorithms that predict the best therapeutic combinations for treating different types of cancer (Abstract #3886/5).
AstraZeneca/MedImmune key presentations at ELCC 2018
|Lead author||Abstract title||Presentation details|
|Planchard D et al.||Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes||ORALAbstract #128OESMO-IASLC Best AbstractsFriday, 13 April 5:30-5:45pmRoom B|
|Leighl N et al.||Patient-reported outcomes from FLAURA: osimertinib versus standard of care (SoC) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC)||POSTER DISCUSSION Abstract #139PD Thursday, 12 April 8:07amRoom A|
|Hui R et al.||Time to deterioration of symptoms with durvalumab in Stage III, locally advanced, unresectable NSCLC: post-hoc analysis of PACIFIC patient-reported outcomes||ORAL Abstract #703 ESMO-IASLC Best AbstractsFriday, 13 April 3:00-5:00pm TBD|
AstraZeneca/MedImmune key presentations at AACR 2018 Annual Meeting
|Lead author||Abstract title||Presentation details|
DNA Damage Response
|Robson M et al.||LynparzaOlympiAD final overall survival: Olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm)||ORALAbstract #CT038Session CTMS01 - New Treatment Approaches for Breast and Ovarian CancerSunday, 15 April 3:50-4:05pmRoom N427 (North, Level 4)|
|Chen Y et al.||Lynparza + ATM inhibitor Adaptive oncology phase 1 study of first-in-class inhibitor of ataxia telangiectasia mutated protein kinase (ATM), in combination with olaparib||POSTERAbstract #4909/5Session PO.ET05.02 - Pharmacokinetics and PharmacodynamicsTuesday, 17 April 1:00-5:00pmHall A, Section 41|
|Krebs M et al.||Lynparza or Imfinzi + ATR inhibitorPhase I study of AZD6738, an inhibitor of ataxia telangiectasia Rad3-related (ATR), in combination with olaparib or durvalumab in patients (pts) with advanced solid cancers||POSTERAbstract #CT026/19Session PO.CT01 - Phase I Clinical Trials 1Sunday, 15 April 1:00-5:00pmHall A, Section 42|
|Leo E et al.||LynparzaA head-to-head comparison of the properties of five clinical PARP inhibitors identifies new insights that can explain both the observed clinical efficacy and safety profiles||POSTERAbstract #LB-273/17Session LBPO.ET03 - Late-Breaking Research: Experimental and Molecular Therapeutics 3 Tuesday, 17 April 1:00-5:00pmHall A, Section 43|
|Lloyd R et al.||Lynparza + ATR inhibitor The PARP inhibitor olaparib is synergistic with the ATR inhibitor AZD6738 in ATM deficient cancer cells||POSTERAbstract #337/18Session PO.MCB07.03 - Cancer Predisposition and Synthetic LethalitySunday, 15 April 1:00-5:00pmHall A, Section 15|
|Young LA et al.||Calquence + ATR inhibitor Pre-clinical efficacy of AZD6738 in combination with the Bruton’s tyrosine kinase inhibitor, Calquence (acalabrutinib), in models of activated B-cell like diffuse large B-cell lymphoma (DLBCL)||POSTERAbstract #LB-263/7Session LBPO.ET03 - Late-Breaking Research: Experimental and Molecular Therapeutics 3Tuesday, 17 April 1:00-5:00pmHall A, Section 43|
|Balar A et al.||Durvalumab + tremelimumab in patients with metastatic urothelial cancer||ORALAbstract #CT112Session CTMS02 - Updates in Immuno-oncology TrialsMonday, 16 April 3:35-3:50pmN Hall C|
|Chaft J et al.||Phase 1b dose-expansion study of the safety and antitumor activity of durvalumab plus tremelimumab in pretreated advanced NSCLC||ORALAbstract #CT113Session CTMS02 - Updates in Immuno-oncology TrialsMonday, 16 April 3:50-4:05pmN Hall C|
|Dovedi SJ et al.||MEDI5752: A novel bispecific antibody that preferentially targets CTLA-4 on PD-1 expressing T-cells||POSTERAbstract #2776/9PO.IM02.11 - Therapeutic Antibodies, Including Engineered Antibodies 2Monday, 16 April 1:00-5:00pmHall A, Section 34|
|O’Donnell P et al.||Updated efficacy and safety profile of durvalumab monotherapy in urothelial carcinoma||POSTERAbstract #CT031/24Session PO.CT01 - Phase I Clinical Trials 1Sunday, 15 April 1:00-5:00pmHall A, Section 42|
Tumour Drivers & Resistance
|Ortiz-Cuaran S et al.||Longitudinal circulating-tumour DNA profiling of EGFR-mutated non-small cell lung cancer patients treated with EGFR-tyrosine kinase inhibitors||ORAL Abstract #937Session MS.CL10.01 - Liquid Biopsy 1Sunday, 15 April 3:20-3:35pmMcCormick Place South (Level 1), Room S105|
|Cidado J et al.||AZD4573, a novel CDK9 inhibitor, rapidly induces cell death in haematological tumour models through depletion of Mcl1||POSTERAbstract #310/17Session PO.MCB02.01 - BCL-2 Family and Mitochondrial ApoptosisSunday, 15 April 1:00-5:00pmHall A, Section 14|
|Flemington V et al.||Combination of the novel ERK inhibitor AZD0364 with the MEK inhibitor selumetinib significantly enhances antitumour activity in KRAS mutant tumour models||POSTERSession PO.ET02.03 - Cell Cycle, Drug Resistance, and CombinationsAbstract #1856/14Monday, 16 April 8:00am-12:00pmHall A, Section 37|
|Simpson I et al.||Discovery of AZD0364, a potent and selective oral inhibitor of ERK1/2 that is efficacious in both monotherapy and combination therapy in models of NSCLC||POSTERAbstract (#1647/2)Session PO.CH01.01 - Target Based Drug DiscoveryMonday, 16 April 8:00am-12:00pmHall A, Section 30|
|Dry JR et al.||A large cancer pharmacogenomics combination screen powering crowd-sourced advancement of computational drug synergy predictions||ORALAbstract #3886/5Session PO.ET05.01 - Pharmacogenetics and Pharmacogenomics Tuesday, 17 April 8:00am-12:00pmHall A, Section 37**part of official press programme|
NOTES TO EDITORS
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 six 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 Oncology as a growth platform for AstraZeneca, 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, Tumour Drivers 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.
MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology; Respiratory, Cardiovascular & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, US., one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK, and Mountain View, US. For more information, please visit www.medimmune.com.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. 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 and follow us on Twitter @AstraZeneca.
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