Gefitinib

Positive results from the DESTINY-Lung04 Phase III trial showed AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC). Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08). In the primary endpoint of PFS, Enhertu monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.50-0.79; p<0.0001). Median PFS was 14.3 months with Enhertu compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favourable PFS trend was seen for Enhertu across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease. Objective response rate (ORR) with Enhertu was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for Enhertu was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy. Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: “HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current first-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy per cent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new first-line treatment option for these patients.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “DESTINY-Lung04 is the first Phase III trial to demonstrate superior progression-free survival versus the global first-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer. These results add to the growing body of evidence supporting Enhertu as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes.” John Tsai, Global Head, R&D, Daiichi Sankyo, said: “Enhertu was the first HER2-directed medicine and antibody drug conjugate approved for patients with HER2-mutant non-small cell lung cancer and has become a second-line standard-of-care treatment. The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of Enhertu in the first-line setting where delaying disease progression for as long as possible is a critical goal.” At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2-directed therapies in the pembrolizumab plus chemotherapy arm versus the Enhertu arm (48.0% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the Enhertu arm (23.8%). The safety profile of Enhertu observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified. Despite longer treatment exposure in the Enhertu arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between Enhertu and pembrolizumab plus chemotherapy (34.1% in the Enhertu arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the Enhertu arm and 14.1% in the pembrolizumab plus chemotherapy arm). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with Enhertu as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low Grade (Grade 1 [n=7; 3.1%] or Grade 2 [n=30; 13.3%]). There were five Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the Enhertu arm. Enhertu is approved to treat patients with previously treated metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumours, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options. Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Notes HER2-mutant NSCLC Lung cancer is the most commonly diagnosed cancer globally and remains the leading cause of cancer-related death.1 In 2024, approximately 2.6 million new lung cancer cases were reported worldwide, with an estimated 1.8 million deaths.1 NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases.2 Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 10% will live beyond five years after diagnosis.3-5 HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface of multiple tumour types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2-4% of patients with non-squamous NSCLC.6-9 These HER2 mutations are predominantly seen in younger women and people with no smoking history and have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.6, 10-14 The global standard of care in the 1st-line metastatic setting of patients with HER2-mutant NSCLC is a combination of immunotherapy and doublet platinum-based chemotherapy.15-17 However, many patients do not respond to 1st-line treatment and experience disease progression, underscoring the need for additional treatment options.18 DESTINY-Lung04 DESTINY-Lung04 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harbouring a HER2 exon 19 or 20 mutation. Patients were randomised 1:1 to receive either Enhertu or standard of care. Randomisation was stratified by smoking history and presence or history of brain metastasis. The primary endpoint of DESTINY-Lung04 is PFS as assessed by BICR. Secondary endpoints include ORR and DOR assessed by BICR and investigator, PFS2 by investigator, OS, pharmacokinetics and safety. DESTINY-Lung04 enrolled 454 patients across multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov. Enhertu Enhertu is a HER2-directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Enhertu (5.4mg/kg) followed by THP is approved in the approved in the US, China, India, Singapore, Brazil and Taiwan as a neoadjuvant treatment for adult patients with HER2-positive (IHC 3+ or ISH+) Stage 2 or Stage 3 breast cancer based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (5.4mg/kg) is approved in the US, Brazil, India and Canada for the adjuvant treatment of adult patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial. Enhertu (5.4mg/kg) in combination with pertuzumab is approved in more than 40 countries worldwide as a 1st-line treatment for adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by a locally or regionally approved test, based on the results from the DESTINY-Breast09 trial. Enhertu (5.4mg/kg) is approved in more than 100 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. Enhertu (5.4mg/kg) is approved in more than 100 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Enhertu (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (6.4mg/kg) is approved in more than 90 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04trials. Enhertu (5.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu clinical development programme A comprehensive global clinical development program is underway evaluating the efficacy and safety of Enhertu as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu and Datroway in collaboration with Daiichi Sankyo; Orpathys in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. 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/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, 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. For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Oncology Corporate and financial

Positive high-level results from a planned interim analysis of the DeLLphi-305 Phase III trial showed Imfinzi (durvalumab) plus Amgen’s Imdelltra® (tarlatamab) demonstrated a statistically significant and highly clinically meaningful improvement in overall survival (OS) versus Imfinzi alone as a 1st-line maintenance treatment. The trial included patients with extensive-stage small cell lung cancer (ES-SCLC) who had not progressed following standard induction treatment with Imfinzi in combination with platinum chemotherapy (investigator’s choice of carboplatin or cisplatin) and etoposide. Imfinzi plus tarlatamab also demonstrated a statistically significant and clinically meaningful improvement in the secondary endpoints of progression-free survival (PFS) and objective response rate. In 2026, an estimated 195,000 people globally will be treated for ES-SCLC, a highly aggressive, fast-growing form of lung cancer characterised by rapid tumour progression and metastatic spread to organs such as the brain and liver.1,2 Immune checkpoint inhibitors such as Imfinzi have led to significant improvements in OS in ES-SCLC, establishing a 1st-line standard of care. However, many patients still experience disease progression due to the aggressive nature of the disease and median OS with the current standard of care is approximately one year.3 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “These results show that Imfinzi-based induction therapy followed by maintenance treatment with Imfinzi plus tarlatamab demonstrates an unprecedented improvement in overall survival for patients with this highly aggressive form of lung cancer. Imfinzi continues to reshape how lung cancer is treated, establishing new standards of care across multiple settings, and these new findings further underscore its role as the backbone immunotherapy of choice for small cell lung cancer.” Jacob Sands, MD, Associate Chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said: “Given the aggressive nature of small cell lung cancer, many patients quickly relapse on current therapy and never reach second-line treatment. These patients do not have time to wait, making substantial progress in the first-line setting critically important. In my career treating people with extensive-stage small cell lung cancer, these are among the most compelling survival results I have seen, indicating the potential to reshape the natural history of small cell lung cancer. DeLLphi-305 represents an unprecedented milestone and suggests we may be entering a new era where meaningfully longer survival is possible for more patients.” Overall, the safety and tolerability profile of Imfinzi plus tarlatamab was consistent with the known safety profiles of the individual treatments, with no new safety signals identified. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Imfinzi is approved in the US, EU, Japan, China and many other countries around the world as the standard-of-care treatment for ES-SCLC and limited-stage SCLC (LS-SCLC) based on the CASPIAN and ADRIATIC Phase III trials, respectively. Notes Small cell lung cancer Lung cancer is the leading cause of cancer death globally, accounting for almost one in five (19%) cancer deaths.4,5 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC.6 About two-thirds of SCLC patients are diagnosed with ES-SCLC, in which the cancer has spread widely through the lung or to other parts of the body.3 While survival rates have improved in recent years following the introduction of immune checkpoint inhibitors, prognosis is still poor, with only 18.1% of LS-SCLC patients and 3.6% of ES-SCLC patients alive five years after diagnosis.2 DeLLphi-305 The DeLLphi-305 trial is sponsored by Amgen, with partial funding and Imfinzi provided by AstraZeneca. It is a global Phase III, randomised, open-label clinical trial evaluating the efficacy and safety of Imfinzi in combination with tarlatamab compared to Imfinzi alone as 1st-line maintenance treatment for patients with ES-SCLC who have not progressed following induction treatment with Imfinzi in combination with platinum chemotherapy and etoposide. Tarlatamab is a first-in-class targeted immunotherapy that binds to both DLL3 on tumour cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells. In the trial, 563 patients who completed Imfinzi-based induction treatment were randomised 1:1 to receive either Imfinzi in combination with tarlatamab or Imfinzi alone until progression or unacceptable toxicity. Following tarlatamab infusion on Cycle 1 Day 1 and Cycle 1 Day 8, patients were monitored in a healthcare setting for 1 to 2 hours (6 to 8 hours in certain regions including Europe). The trial included patients with both treated and untreated asymptomatic brain metastases at baseline. The primary endpoint is OS for Imfinzi plus tarlatamab versus Imfinzi alone. PFS is a key secondary endpoint. Imfinzi Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses. In addition to its indications in SCLC, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). It is also approved as a monotherapy in unresectable HCC in Japan, China and the EU, and in resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers in the US and the EU. Additionally, in April 2026, Imfinzi in combination with Imjudo, lenvatinib and transarterial chemoembolisation (TACE) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS versus TACE alone for patients with unresectable HCC eligible for embolisation in the EMERALD-3 Phase III trial. Perioperative Imfinzi in combination with neoadjuvant chemotherapy is approved for cisplatin-eligible muscle-invasive bladder cancer (MIBC). Imfinzi in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy is approved in the US and other countries for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer. In May 2026, positive high-level results from the VOLGA Phase III trial showed that perioperative treatment with Imfinzi in combination with neoadjuvant enfortumab vedotin (EV) demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and OS in patients with MIBC who were ineligible for or had declined cisplatin-based chemotherapy. In addition, perioperative Imfinzi plus Imjudo in combination with neoadjuvant EV demonstrated a statistically significant and clinically meaningful improvement in EFS and a favourable trend for OS; however, the OS data were not statistically significant at this planned interim analysis and will be formally reassessed at a subsequent analysis. In July 2026, positive high-level results from the NILE Phase III trial showed Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS versus chemotherapy as 1st-line treatment for patients with PD-L1 high unresectable, locally advanced or metastatic urothelial cancer. Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US, EU and China). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017,more than 470,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi and Imjudo; Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. 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/NYSE: 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. References Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial