AstraZeneca advances ambition to improve standards of care in multiple cancer types at WCLC and ESMO 2024

Presidential Symposium will demonstrate how proprietary computational pathology biomarker for TROP2 enhances patient selection and potentially predicts patient outcomes in advanced lung cancer. Presidential Symposium for NIAGARA will highlight practice-changing impact of a perioperative Imfinzi-based regimen in bladder cancer.

AstraZeneca advances its ambition to revolutionise cancer care with new data across its diverse, industry-leading portfolio and pipeline at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer, 7 to 10 September 2024 and the European Society for Medical Oncology (ESMO) Congress, 13 to 17 September 2024.

Across the two meetings, more than 130 abstracts will feature 17 approved and potential new medicines from AstraZeneca including five Presidential Symposia and 41 oral presentations.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The presentations across these two congresses advance our long-term strategy to revolutionise cancer care. We will show results from our computational pathology platform at WCLC which we are using across our antibody drug conjugate portfolio to develop predictive biomarkers to enhance patient selection and improve outcomes for patients. We will also share data on the use of our TROP2 antibody drug conjugate datopotamab deruxtecan in combination with Imfinzi in early-stage lung cancer, a promising first look at clinical activity from two of our own pipeline antibody drug conjugates and important progress for our next-generation immunotherapies.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Our data featured at WCLC and ESMO will exhibit AstraZeneca’s progress in advancing several of the biggest trends transforming cancer treatment today and potentially in the future. Positive results for Imfinzi from the NIAGARA trial in muscle-invasive bladder cancer will show the importance of integrating perioperative immunotherapy in this setting, and data for datopotamab deruxtecan and Enhertu in several lung cancer settings will highlight how antibody drug conjugates have the potential to replace traditional chemotherapy approaches in many cancer settings.”  

Key trend: early intervention and transforming outcomes in early-stage disease

A Presidential Symposium at ESMO will showcase the results from the NIAGARA Phase III trial of Imfinzi (durvalumab) in combination with neoadjuvant chemotherapy before cystectomy (surgery to remove the bladder) followed by Imfinzi as adjuvant monotherapy in patients with muscle-invasive bladder cancer. High-level results for this Imfinzi-based regimen showed a statistically significant and clinically meaningful event-free survival (EFS) and overall survival (OS) benefit, making it the first perioperative immunotherapy regimen to show extended survival in bladder cancer in a Phase III trial.

In lung cancer, several presentations at both meetings will reinforce the Company’s progress toward moving treatment to earlier stages of disease. These include:

• A late-breaking Presidential Symposium at WCLC that will feature efficacy and safety data from the NeoCOAST-2 Phase II platform trial. This trial evaluates Imfinzi in multiple novel combinations, before and after surgery, in patients with resectable, early-stage non-small cell lung cancer (NSCLC), including a combination with datopotamab deruxtecan. Results will build on the proven efficacy of perioperative Imfinzi as demonstrated in the AEGEAN Phase III trial, which was recently approved in the US.

• A late-breaking oral presentation at WCLC sharing results from the second interim analysis of the AEGEAN Phase III trial of perioperative Imfinzi-based treatment in patients with resectable early-stage (IIA-IIIB) NSCLC. The data include EFS in subgroups of patients who did or did not achieve pathologic complete response, as well as new disease-free survival and OS results. An additional late-breaking oral presentation at ESMO sharing AEGEAN circulating tumour DNA (ctDNA) data will provide insights on how patients respond to treatment.

• A late-breaking mini-oral presentation at WCLC highlighting patient-reported outcomes from the ADRIATIC Phase III trial of Imfinzi in patients with limited-stage small cell lung cancer whose disease did not progress on concurrent chemoradiotherapy (CRT). Additionally, an oral presentation at ESMO will share outcomes in key patient subgroups.

• A mini-oral presentation at ESMO of results from the LAURA Phase III trial including analyses of central nervous system metastases and distant progression with Tagrisso (osimertinib) in unresectable, Stage III EGFRm NSCLC after CRT. Additional data from LAURA will include a safety analysis at WCLC and a poster presentation at ESMO of efficacy and safety results in a cohort of patients in China.

Key trend: novel ADCs replacing systemic chemotherapy

A late-breaking Presidential Symposium at WCLC of exploratory results from the application of AstraZeneca’s proprietary computational pathology platform, quantitative continuous scoring (QCS), to tissue samples collected in TROPION-Lung01 will demonstrate the potential of TROP2, as measured by QCS, as a predictive biomarker for datopotamab deruxtecan.

Additionally, a late-breaking oral presentation will showcase OS data from the TROPION-Lung01 Phase III trial evaluating datopotamab deruxtecan in patients with previously treated locally advanced or metastatic NSCLC. In May, high-level results showed that datopotamab deruxtecan demonstrated a clinically meaningful OS improvement versus docetaxel, the current standard-of-care chemotherapy, in patients with advanced nonsquamous NSCLC previously treated with immunotherapy or targeted therapy.

Also, at WCLC, an oral presentation will highlight efficacy and safety data from Part 1 of the DESTINY-Lung03 Phase Ib trial of Enhertu (trastuzumab deruxtecan) in patients with previously treated HER2-overexpressing unresectable, locally advanced or metastatic NSCLC, building on data from the DESTINY-Lung01 Phase II trial.

At ESMO, a late-breaking oral presentation from the DESTINY-Breast12 Phase IIIb/IV trial of Enhertu in patients with previously treated metastatic HER2-positive breast cancer with and without brain metastases will showcase the potential benefits of this important medicine in this patient population. Additionally, an oral presentation of the DESTINY-Gastric03 Phase Ib/II trial will feature safety and efficacy data for the combination of Enhertu, chemotherapy and pembrolizumab as a 1st-line treatment in HER2-positive gastric and gastroesophageal junction (GEJ) cancers.

A mini-oral presentation at ESMO will highlight first results from the endometrial and ovarian cancer cohorts of the TROPION-PanTumour03 Phase II trial of datopotamab deruxtecan.

Several presentations at ESMO will showcase the strength of the Company’s emerging proprietary antibody drug conjugate (ADC) technology. These include:

• A proffered paper presentation sharing dose escalation results from the BLUESTAR Phase I/IIa trial of B7-H4 ADC AZD8205 in patients with B7-H4-expressing advanced solid tumours. B7-H4 is a promising ADC target which is highly expressed in several solid tumours. AZD8205 is the first ADC bearing a novel proprietary topoisomerase I inhibitor (TOP1i) linker payload to enter the clinic. Robust AZD8205 anti-tumour response has previously been reported in B7-H4-expressing preclinical models across multiple tumour types.

• A poster presentation sharing dose escalation results from the FONTANA Phase I/IIa first-in-human trial of AZD5335 demonstrating clinical activity, favourable pharmacokinetic and manageable safety profiles in patients with platinum-resistant recurrent ovarian cancer. This ADC has a FRα-targeting antibody linked to a proprietary TOP1i warhead. A robust anti-tumour response has previously been reported in FRα-expressing preclinical models that are resistant to another FRα ADC with a microtubule inhibitor warhead.

Key trend: advancing next wave of immunotherapy agents

Several presentations will underscore the Company’s commitment to advancing its comprehensive bispecific antibody programme:

• A poster presentation sharing the first report of overall response rate and safety data from Substudy 2 of the GEMINI-Gastric Phase II trial, testing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific immune checkpoint inhibitor, plus chemotherapy as a 1st-line treatment in patients with HER2-negative, locally advanced unresectable or metastatic GEJ cancers.
• Additionally, two late-breaking oral presentations at WCLC will highlight efficacy and safety results from the ARTEMIDE-01 Phase I trial of rilvegostomig in patients with metastatic NSCLC, as well as from a Phase Ib/II trial of volrustomig (PD-1/CTLA-4) in combination with chemotherapy in the 1st-line for patients with advanced NSCLC. 

Key trend: powerful combinations to attack cancer from multiple angles

In addition to the novel regimens evaluated in DESTINY-Lung03, DESTINY-Gastric03 and NeoCOAST-2, we are assessing further combination treatment approaches below to improve outcomes for patients:

• A late-breaking, Presidential Symposium presentation for Tagrisso from the externally sponsored FLOWERS Phase II trial of Tagrisso with or without Orpathys (savolitinib) in patients with EGFRm advanced NSCLC with MET aberrations will evaluate the potential of this novel combination to overcome mechanisms of resistance in the 1st-line setting.

• Two late-breaking mini-oral presentations at WCLC will highlight new data from the FLAURA2 Phase III trial of Tagrisso plus chemotherapy in advanced EGFRm NSCLC, including efficacy in patients with high tumour burden and those whose cancers harbour TP53 mutations at baseline.

• A mini-oral presentation featuring five-year OS data from an exploratory analysis of the HIMALAYA Phase III trial of STRIDE (Single Tremelimumab Regular Interval Durvalumab) in patients with unresectable liver cancer who have not received prior systemic therapy and are not eligible for localised treatment. These data represent the longest survival follow-up reported to date for a Phase III trial in this setting.

Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with Daiichi Sankyo Company Limited to develop and commercialise Enhertu and datopotamab deruxtecan, collaborating with MSD (Merck & Co., Inc. in the US and Canada) to develop and commercialise Lynparza (olaparib), and collaborating with HUTCHMED to develop and commercialise Orpathys. Rilvegostomig is a PD-1/TIGIT bispecific antibody where the TIGIT component is derived from Compugen’s clinical stage anti-TIGIT antibody, COM902. AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialisation agreement initiated in 2015.

Key AstraZeneca presentations during IASLC WCLC 2024¹

Lead Author	Abstract Title	Presentation details (PDT)
Antibody drug conjugates
Garassino, MC	Normalized membrane ratio of TROP2 by quantitative continuous scoring is predictive of clinical outcomes in TROPION-Lung 01	Abstract #PL02.11 Presidential 1 8 September 2024  9:22 AM
Sands, J	Datopotamab deruxtecan vs docetaxel in patients with non-small cell lung cancer: final overall survival from TROPION-Lung01	Abstract #OA08.03 Oral Session 9 September 2024 10:47 AM
Planchard, D	Trastuzumab deruxtecan monotherapy in pretreated HER2-overexpressing nonsquamous non-small cell lung cancer: DESTINY-Lung03 part 1	Abstract #OA16.05 Oral Session 10 September 2024  1:52 PM
Immuno-oncology
Cascone, T	Neocoast-2: Efficacy and safety of neoadjuvant durvalumab (D) + novel anticancer agents + CT and adjuvant D ± novel agents in resectable NSCLC	Abstract #PL02.07 Presidential 1  8 September 2024 8:56 AM
Hiltermann, TJN	Efficacy and safety of rilvegostomig, an anti-PD-1/TIGIT bispecific, for CPI-naïve metastatic NSCLC with PD-L1 1-49% or ≥50%	Abstract #OA11.03 Oral Session 9 September 20242:02 PM
Heymach, JV	Perioperative durvalumab for resectable NSCLC (R-NSCLC): updated outcomes from the phase 3 AEGEAN trial	Abstract #OA13.03 Oral Session 9 September 2024 3:32 PM
Spigel, DR	Volrustomig + platinum doublet chemotherapy (CTx) in first-line non-small cell lung cancer (NSCLC): phase 1b trial update	Abstract #OA11.04 Oral Session 9 September 2024 2:12 PM
Novello, S	Patient-reported outcomes (PROs) with consolidation durvalumab versus placebo following cCRT in limited-stage SCLC: ADRIATIC	Abstract #MA17.04 Mini Oral Session 10 September 2024 3:07 PM
Skoulidis, F	TRITON: Tremelimumab + durvalumab + chemotherapy (CT) vs pembrolizumab + CT in mNSCLC with STK11, KEAP1 and/or KRAS mutations	Abstract #P4.11D.01 Poster Session 9 September 2024 6:30 PM
Tumour drivers and resistance
Yang, J	Osimertinib with or without savolitinib as 1L in de novo MET aberrant, EGFRm advanced NSCLC (CTONG 2008): a phase II trial	Abstract #PL04.10 Presidential 2 9 September 2024 9:17 AM
Kato, T	Osimertinib after definitive CRT in unresectable stage III EGFR-mutated NSCLC: safety outcomes from the phase 3 LAURA study	Abstract #OA12.03 Oral Session 9 September 2024 2:02 PM
Yang, JC	FLAURA2: Resistance, and impact of baseline TP53 alterations in patients treated with 1L osimertinib ± platinum-pemetrexed	Abstract #MA12.03 Mini Oral Session 10 September 2024 1:32 PM
Valdiviezo, N	FLAURA2: Impact of tumor burden on outcomes of 1L osimertinib ± chemotherapy in patients with EGFR-mutated advanced NSCLC	Abstract #MA12.04 Mini Oral Session 10 September 2024 1:37 PM

¹ 59 abstracts at IASLC WCLC 2024 will feature AstraZeneca medicines and pipeline molecules

Key AstraZeneca presentations during ESMO Congress 2024²

Lead Author	Abstract Title	Presentation details (CEST)
Antibody drug conjugates
Datopotamab deruxtecan
Oaknin, A	Datopotamab deruxtecan (Dato-DXd) in patients with endometrial (EC) or ovarian cancer (OC): results from the phase 2 TROPION-PanTumor03 study	Abstract #714MO Mini Oral Session15 September 2024 2:45 PM
Trivedi, MS	Rates of pathologic complete response (pCR) after datopotamab deruxtecan (dato) plus durvalumab (durva) treatment strategy in the neoadjuvant setting: results from the I-SPY 2.2 trial	Abstract #LBA15 Mini Oral Session 14 September 2024 11:20 AM
Khoury, K	Rates of pathologic complete response (pCR) after datopotamab deruxtecan (dato) in the neoadjuvant setting: results from the I-SPY 2.2 trial	Abstract #LBA16 Mini Oral Session 14 September 2024 11:25 AM
Rugo, HS	Exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) from the TROPION-Breast01 study of datopotamab deruxtecan (Dato-DXd) vs investigator’s choice of chemotherapy (ICC) in patients (pts) with pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC)	Abstract #431P Poster Session 16 September 2024
Pons-Tostivint, E	Datopotamab deruxtecan (Dato-DXd) vs docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with brain metastases (mets): results from TROPION-Lung01	Abstract #1312P Poster Session 14 September 2024
Enhertu
Lin, N	Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results	Abstract #LBA18 Proffered Paper Session 13 September 2024 4:00 PM
Janjigian, YY	Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03)	Abstract #1401O Proffered Paper Session 14 September 2024 9:25 AM
Hu, X	Effects of trastuzumab deruxtecan (T-DXd) vs choice of chemotherapy (TPC) on patient-reported outcomes (PROs) in hormone receptor–positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC): results from DESTINY-Breast06	Abstract #LBA22 Mini Oral Session 15 September 2024 9:10 AM
Ueno, NT	Exploratory biomarker analysis of trastuzumab deruxtecan versus treatment of physician’s choice in HER2-low, hormone receptor–positive metastatic breast cancer in DESTINY-Breast04	Abstract #432P Poster Session 16 September 2024
AZD8205
Meric-Bernstam, F	Initial results from a first-in-human study of the B7-H4–directed antibody-drug conjugate (ADC) AZD8205 (puxitatug samrotecan) in patients with advanced/metastatic solid tumors	Abstract #606O Proffered Paper Session 13 September 2024 4:50 PM
AZD5335
Shapira-Frommer, R	Initial results from a first-in-human study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug conjugate, in patients (pts) with platinum-resistant recurrent ovarian cancer (PRROC)	Abstract #754P Poster Session 14 September 2024
Immuno-oncology
Powles, TB	A randomized phase 3 trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA)	Abstract #LBA5 Presidential 215 September 2024 5:14 PM
Tomasini, P	Precision immuno-oncology for advanced non-small cell lung cancer (NSCLC) patients with PD-(L)1 inhibitors resistance (PIONeeR): a phase Ib/IIa clinical trial targeting identified resistance pathways	Abstract #LBA8 Presidential 316 September 2024 5:24 PM
Senan, S	Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial	Abstract #LBA81 Proffered Paper Session 13 September 2024 2:25 PM
Reck, M	Associations of ctDNA clearance (CL) during neoadjuvant Tx with pathological response and event-free survival (EFS) in pts with resectable NSCLC (R-NSCLC): expanded analyses from AEGEAN	Abstract #LBA49 Mini Oral Session 15 September 2024 10:40 AM
Riccardo Filippi, A	Circulating tumor DNA (ctDNA) dynamics and treatment responses in chemotherapy-ineligible patients (pts) with unresectable Stage III NSCLC from the phase 2 DUART trial	Abstract #LBA51 Mini Oral Session 15 September 2024 10:45 AM
Rimassa, L	Five-year overall survival (OS) and OS by tumour response measures from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)	Abstract #947MO Mini Oral Session 16 September 2024 9:25 AM
Rivera Herrero, F	First-line rilvegostomig (rilve) + chemotherapy (CTx) in patients (pts) with HER2-negative (HER2–) locally advanced unresectable or metastatic gastric cancers: first report of GEMINI-Gastric substudy 2	Abstract #1422P Poster Session 16 September 2024
Blank, SV	Durvalumab + carboplatin/paclitaxel (CP) followed by durvalumab ± olaparib as a first-line treatment for endometrial cancer (EC): progression-free survival (PFS) by clinical factors in DUO-E	Abstract #732P Poster Session 14 September 2024
Tumour drivers and resistance
Lu, S	Osimertinib (osi) after definitive chemoradiotherapy (CRT) in unresectable (UR) stg III EGFRm NSCLC: analyses of CNS and distant progression from the phase 3 LAURA study	Abstract #1241MO Mini Oral Session 16 September 2024  2:45 PM
Dong, X	Osimertinib (osi) after definitive chemoradiotherapy (CRT) in unresectable stage III epidermal growth factor receptor-mutated (EGFRm) NSCLC: LAURA China cohort analysis	Abstract #1248P Poster Session 14 September 2024

² 79 abstracts at ESMO Congress 2024 will feature AstraZeneca medicines and pipeline molecules

Notes

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care 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 in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.

Contacts
For details on how to contact the Investor Relations Team, please click here. For media contacts, click here.