AstraZeneca will present new data from across the innovative lung cancer portfolio at the IASLC 2020 World Conference on Lung Cancer (WCLC), hosted by the International Association for the Study of Lung Cancer, 28 to 31 January 2021.

Eleven AstraZeneca medicines and potential new medicines from the pipeline feature in 39 abstracts showcasing the Company's leadership across different types and stages of lung cancer, including eight oral presentations with two late breakers.

• Updated data from the TROPION-PanTumor01 Phase I trial of datopotamab deruxtecan (Dato-DXd; DS-1062) with additional patients, supporting its potential to redefine treatment outcomes in advanced non-small cell lung cancer (NSCLC). Datopotamab deruxtecan is a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC)
• New data from the DESTINY-Lung01 Phase II trial highlighting the potential of Enhertu (trastuzumab deruxtecan) in HER2-expressing metastatic NSCLC, and data in metastatic HER2-mutant (HER2m) NSCLC, two groups of patients for whom no HER2-directed medicine is currently approved
• New analyses from the ADAURA Phase III trial featured in two oral presentations reinforcing the unprecedented benefit of Tagrisso (osimertinib) regardless of prior adjuvant chemotherapy or disease stage in the adjuvant treatment of epidermal growth factor receptor-mutated (EGFRm) NSCLC, and showing patients treated with Tagrisso maintained their quality of life

José Baselga, Executive Vice President, Oncology R&D, said: "AstraZeneca is leading the next wave of precision-medicine innovations in lung cancer that aim to change clinical practice and ultimately alter the course of the disease. Our data at WCLC for datopotamab deruxtecan and Enhertu illustrate the potentially transformative role next-generation antibody drug conjugates may play in advanced non-small cell lung cancer. New results for Tagrisso and Imfinzi continue to validate our strategy to treat patients earlier, as we progress the science of identifying patients most likely to respond to treatment."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "AstraZeneca is committed to advancing early detection and treatment of lung cancer - and the urgency to achieve this goal has only increased during the pandemic, which has significantly impacted cancer care for patients around the world. Our Tagrisso and Imfinzi data at WCLC show how we are driving progress in early-stage lung cancer, while also pushing the scientific boundaries in resistant and advanced disease to identify new solutions for patients."

Harnessing the emerging potential of ADCs to treat different types of lung cancer

Updated data from the TROPION-PanTumor01 Phase I trial of the novel ADC datopotamab deruxtecan will be featured in an oral presentation, demonstrating early antitumour activity in patients with advanced/metastatic NSCLC who had progressed on standard treatment. Additionally, two presentations on the data from the DESTINY-Lung01 Phase II trial will show results of Enhertu patients with NSCLC, including new data from the HER2-expressing cohort and data from the HER2 mutant cohort.

Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialise Enhertu and datopotamab deruxtecan globally.

Treating patients with NSCLC in early stages

A late-breaking analysis from the ADAURA Phase III trial will underscore the practice-changing results for adjuvant Tagrisso in Stage IB-IIIA EGFRm NSCLC and show the disease-free survival benefit for patients who had been treated with adjuvant chemotherapy prior to Tagrisso and those who were not by stage of disease. A second exploratory analysis from the Phase III ADAURA trial will highlight the impact of treatment with adjuvant Tagrisso on quality of life based on patient-reported outcomes. Tagrisso was recently approved (https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/tagrisso-approved-in-the-us-for-early-lung-cancer.html) in the adjuvant setting in the US.

The ongoing NeoADAURA Phase III trial testing the benefit of treating patients with resectable EGFRm NSCLC with neoadjuvant Tagrisso will be highlighted in a poster presentation.

The MERMAID-1 Phase III trial testing Imfinzi (durvalumab) in patients with completely resected, Stage II and III NSCLC who show evidence of minimal residual disease (MRD), will also be highlighted in a poster. MERMAID-1 is an early-stage NSCLC Phase III trial evaluating circulating tumour DNA measurements to monitor for MRD and to identify patients at high risk of recurrence after surgery who may benefit from intervention with immunotherapy.

Progressing research in advanced lung cancer

• Additional data from the CASPIAN Phase III trial of Imfinzi in extensive-stage small cell lung cancer (ES-SCLC) showing exposure response and pharmacokinetics as well as exploratory analyses based on extent of disease
• The biomarker-directed HUDSON Phase II platform trial of Imfinzi in combination with Lynparza (olaparib) and other novel anti-cancer medicines, including danvatirsen (STAT3 antisense oligonucleotide), ceralasertib (ATR inhibitor) and oleclumab (anti-CD73), in patients with NSCLC who progressed on anti-PD(L)1 therapy
• The ODIN BM Phase I trial assessing Tagrisso brain exposure in patients with EGFRm NSCLC central nervous system (CNS) metastases
• The TATTON Phase Ib trial of Tagrisso plus savolitinib in patients with EGFRm MET-overexpressed/amplified NSCLC
• A trial-in-progress update on the Phase I trial of Tagrisso in combination with patritumab deruxtecan (HER3-DXd; U3-1402) in patients with locally advanced or metastatic EGFRm NSCLC

Key AstraZeneca presentations during WCLC 2020[1]

[][][][]
Lead Abstract title Presentation details
author
Immuno
-Oncology
Reinmuth, First-line durvalumab Abstract #P48.03Poster: P48 - Small Cell
N plus platinum-etoposide Lung Cancer/NET - Chemo - IO 28 January
in ES-SCLC: exploratory 2021
analyses based on
extent of disease in
CASPIAN
Zheng, Y Population Abstract #P48.21Poster: P48 - Small Cell
pharmacokinetics and Lung Cancer/NET - Chemo - IO
exposure-response with 28 January 2021
durvalumab plus
platinum-etoposide in
ES-SCLC: Results from
CASPIAN
Besse, B HUDSON: An open-label, Abstract #OA07.08Oral Session: OA07 -
multi-drug, biomarker Immuno-biology and Novel
-directed Phase II Immunotherapeutics from Bench to Bed30
platform study in January 2021
patients with NSCLC, 11:05-11:10 SGT
who progressed on anti
-PD(L)1 therapy
Besse, B Immuno-modulatory Abstract #P16.07Poster: P16 - Immuno
effects of ceralasertib -biology and Novel Immunotherapeutics
in combination with (Phase I and Translational)
durvalumab in NSCLC
with progression on
anti-PD(L)1 treatment
(HUDSON)
Peters, S MERMAID-1: A Phase III Abstract #P03.03Poster: P03 - Early
study of adjuvant Stage/Localized Disease - Clinical Trials
durvalumab plus in Progress
chemotherapy in 28 January 2021
resected NSCLC patients
with MRD+ post-surgery
Tumour
drivers
and
resistance
Wu, Y-L Postoperative Abstract #OA06.04Oral Session: OA06 -
chemotherapy use and Updates on EGFR Targeted Perioperative
outcomes from ADAURA: Therapy and Precision Adjuvant
osimertinib as adjuvant Chemotherapy29 January 202116:55-17:05
therapy for resected SGT
EGFR mutated NSCLC
Majem, M Patient-reported Abstract #OA06.03Oral Session: OA06 -
outcomes from ADAURA: Updates on EGFR Targeted Perioperative
osimertinib as adjuvant Therapy and Precision Adjuvant
therapy in patients Chemotherapy 29 January 202116:45-16:55
with resected EGFR SGT
mutated (EGFRm) NSCLC
Tsuboi, M Neoadjuvant osimertinib Abstract #P03.02Poster: P03 - Early
with/without Stage/Localized Disease - Clinical Trials
chemotherapy vs in Progress
chemotherapy for EGFR 28 January 2021
mutated resectable
NSCLC: neoADAURA
Cho, BC ORCHARD: A biomarker Abstract #P76.27Poster: P76 - Targeted
-directed Phase 2 Therapy - Clinically Focused - EGFR
platform study in pts 28 January 2021
with advanced EGFRm
NSCLC progressing on
first-line osimertinib
Jänne, PA Phase 1 study of Abstract #P01.03Poster: P01 - Antibody
patritumab deruxtecan Drug Conjugates, Novel Therapeutics and
(HER3-DXd; U3-1402) in Cytotoxics
combination with 28 January 2021
osimertinib in patients
with locally advanced
or metastatic EGFR
-mutated NSCLC[2]
Han, J-Y Osimertinib+savolitinib Abstract #FP14.03Featured Poster Session:
in pts with EGFRm MET FP14 - Targeted Therapy - Clinically
-amplified/overexpressed Focused 28 January 2021
NSCLC: Phase Ib TATTON
parts B and D final
analysis
Ekman, S A PET and MRI study Abstract #P76.72Poster: P76 - Targeted
exploring osimertinib Therapy - Clinically Focused - EGFR 28
brain exposure and January 2021
efficacy in EGFRm NSCLC
CNS metastases
Antibody
drug
conjugates
Spira, A Datopotamab deruxtecan Abstract #OA03.03Oral Session: OA03 -
(dato-DXd; DS-1062), a Promising Antibody-Drug Conjugate and
TROP2 ADC, in patients Cytotoxic Therapy in NSCLC29 January
with advanced NSCLC: 202110:30-10:40 SGT
updated results of
TROPION-PanTumor01
Phase 1 study[3]
Nakagawa, Trastuzumab deruxtecan Abstract #OA04.05Oral Session: OA04 - New
K in HER2-overexpressing Data from Rare EGFR Alterations29 January
metastatic non-small 202112:05-12:15 SGT
cell lung cancer:
interim results of
DESTINY-Lung01[3]
Smit, EF Trastuzumab deruxtecan Abstract #MA11.03Mini Oral Session: MA11
in HER2-mutated - Expanding Targetable Genetic
metastatic non-small Alterations in NSCLC31 January 202114:15
cell lung cancer -14:20 SGT
(NSCLC): interim
results of DESTINY
-Lung01[3]

[1]39 abstracts at WCLC 2020 will feature AstraZeneca medicines and pipeline molecules, of which 24 are company-sponsored or supported.

[2]Trial collaboration with Daiichi Sankyo which maintains exclusive rights to patritumab deruxtecan.

[3]Enhertu and datapotamab deruxtecan are developed and commercialised in collaboration with Daiichi Sankyo worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

AstraZeneca aims to address the unmet needs of patients with EGFRm tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines Iressa (gefitinib) and Tagrisso and its ongoing LAURA, NeoADAURA and FLAURA2 Phase III trials.[1-3] AstraZeneca is committed to addressing tumour mechanisms of resistance through the ongoing SAVANNAH and ORCHARD Phase II trials, which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

The Company is also evaluating the potential of ADCs to improve patient outcomes in tumours with targetable gene alterations, including HER2m NSCLC which affects approximately 2-4% of patients with NSCLC.[4,5] Enhertu, a HER2-directed antibody drug conjugate, is in development for metastatic non-squamous HER2-overexpressing or HER2m NSCLC including trials in combination with other anticancer treatments. In addition, a broad and comprehensive clinical development programme is evaluating the efficacy and safety of datopotamab deruxtecan (a TROP2-directed ADC) across multiple TROP2 cancers, as both a monotherapy and in combination with other anticancer treatments.

An extensive Immuno-Oncology (IO) development programme focuses on lung cancer patients without a targetable genetic mutation, which represent up to three-quarters of all patients with lung cancer.[6] Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (POSEIDON and PEARL Phase III trials) and for patients in earlier stages of disease, including potentially curative settings (MERMAID-1, MERMAID-2, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC Phase III trials) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Imfinzi is also in development in the NeoCOAST, COAST and HUDSON Phase II trials in combination with potential new medicines from the early-stage pipeline, including Enhertu.

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 seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - 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.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) 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 & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca).

References

1. Szumera-Ciećkiewicz A, et al. EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence. Int J Clin Exp Pathol. 2013;6:2800-12.

2. Keedy VL, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011;29:2121-27.

3. Ellison G, et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol. 2013;66:79-89.

4. Campbell JD, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016;48(6):607-16.

5. Li BT, et al. HER2 amplification and HER2 mutation are distinct molecular targets in lung cancers. J Thorac Oncol. 2016;11(3): 414-419.

6. Pakkala, S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3(15):e120858.