On April 4, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported it 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) (Free AACR Whitepaper) annual meeting in Chicago,14-18 April (Press release, AstraZeneca, APR 4, 2018, View Source [SID1234525172]). 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.
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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 (Free AACR Whitepaper) meeting, we will share pioneering early science across multiple tumour types."
ELCC
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).
Immuno-Oncology (IO)
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).
Crowd-sourcing combinations
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
Tagrisso (osimertinib)
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
ORAL
Abstract #128O
ESMO-IASLC Best Abstracts
Friday, 13 April
5:30-5:45pm
Room 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
8:07am
Room A
Imfinzi
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 Abstracts
Friday, 13 April
3:00-5:00pm TBD
AstraZeneca/MedImmune key presentations at AACR (Free AACR Whitepaper) 2018 Annual Meeting
Lead author
Abstract title
Presentation details
DNA Damage Response
Robson M et al.
Lynparza
OlympiAD 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)
ORAL
Abstract #CT038
Session CTMS01 – New Treatment Approaches for Breast and Ovarian Cancer
Sunday, 15 April
3:50-4:05pm
Room 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
POSTER
Abstract #4909/5
Session PO.ET05.02 – Pharmacokinetics and Pharmacodynamics
Tuesday, 17 April
1:00-5:00pm
Hall A, Section 41
Krebs M et al.
Lynparza or Imfinzi + ATR inhibitor
Phase 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
POSTER
Abstract #CT026/19
Session PO.CT01 – Phase I Clinical Trials 1
Sunday, 15 April
1:00-5:00pm
Hall A, Section 42
Leo E et al.
Lynparza
A 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
POSTER
Abstract #LB-273/17
Session LBPO.ET03 – Late-Breaking Research: Experimental and Molecular Therapeutics 3
Tuesday, 17 April
1:00-5:00pm
Hall 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
POSTER
Abstract #337/18
Session PO.MCB07.03 – Cancer Predisposition and Synthetic Lethality
Sunday, 15 April
1:00-5:00pm
Hall 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)
POSTER
Abstract #LB-263/7
Session LBPO.ET03 – Late-Breaking Research: Experimental and Molecular Therapeutics 3
Tuesday, 17 April
1:00-5:00pm
Hall A, Section 43
Immuno-Oncology
Balar A et al.
Durvalumab + tremelimumab in patients with metastatic urothelial cancer
ORAL
Abstract #CT112
Session CTMS02 – Updates in Immuno-oncology Trials
Monday, 16 April
3:35-3:50pm
N 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
ORAL
Abstract #CT113
Session CTMS02 – Updates in Immuno-oncology Trials
Monday, 16 April
3:50-4:05pm
N Hall C
Dovedi SJ et al.
MEDI5752: A novel bispecific antibody that preferentially targets CTLA-4 on PD-1 expressing T-cells
POSTER
Abstract #2776/9
PO.IM02.11 – Therapeutic Antibodies, Including Engineered Antibodies 2
Monday, 16 April
1:00-5:00pm
Hall A, Section 34
O’Donnell P et al.
Updated efficacy and safety profile of durvalumab monotherapy in urothelial carcinoma
POSTER
Abstract #CT031/24
Session PO.CT01 – Phase I Clinical Trials 1
Sunday, 15 April
1:00-5:00pm
Hall 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 #937
Session MS.CL10.01 – Liquid Biopsy 1
Sunday, 15 April
3:20-3:35pm
McCormick 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
POSTER
Abstract #310/17
Session PO.MCB02.01 – BCL-2 Family and Mitochondrial Apoptosis
Sunday, 15 April
1:00-5:00pm
Hall 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
POSTER
Session PO.ET02.03 – Cell Cycle, Drug Resistance, and Combinations
Abstract #1856/14
Monday, 16 April
8:00am-12:00pm
Hall 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
POSTER
Abstract (#1647/2)
Session PO.CH01.01 – Target Based Drug Discovery
Monday, 16 April
8:00am-12:00pm
Hall A, Section 30
Innovative Methodologies
Dry JR et al.
A large cancer pharmacogenomics combination screen powering crowd-sourced advancement of computational drug synergy predictions
ORAL
Abstract #3886/5
Session PO.ET05.01 – Pharmacogenetics and Pharmacogenomics
Tuesday, 17 April
8:00am-12:00pm
Hall A, Section 37*
*part of official press programme