WILMINGTON, Del. / Mar 25, 2025 / Business Wire / New study results presented at the European Lung Cancer Congress (ELCC) 2025, March 26 to 29, demonstrate the role of AstraZeneca’s TAGRISSO® (osimertinib), as monotherapy and as the backbone for novel combinations, across stages and settings of epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Highlights include:
Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, said: “A critical goal in treating every patient with lung cancer is to not only extend a patient's life but also maintain quality of life while on treatment. The continued overall survival trend seen here at ELCC in the unresectable Stage III setting and the promising data for combinations that can address progression in the advanced setting, together reinforce osimertinib as an effective, safe and convenient treatment for patients with EGFR-mutated lung cancer across stages and lines of treatment.”
Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca, said: “Having now treated more than one million patients around the world, TAGRISSO has repeatedly transformed expectations for patients with EGFR-mutated lung cancer by not only extending survival but also showing it is possible to maintain quality of life during cancer treatment. The breadth of data at ELCC reinforce TAGRISSO as the backbone therapy for patients with this disease and show that adding savolitinib or datopotamab deruxtecan-dlnk at the time of disease progression can help prolong patients’ responses to treatment.”
Professor Virginia Harrison, EGFR Positive UK, said: “For people undergoing treatment for lung cancer, maintaining quality of life is so important, but it can be challenging. The development of simple and effective treatment regimens that minimize negative side effects can make a huge difference. We are excited to see this progress for patients with EGFR-mutated lung cancer, where there is still significant unmet need.”
TAGRISSO continued to demonstrate encouraging overall survival (OS) trend in unresectable, Stage III setting in LAURA trial
Updated results from the LAURA Phase III trial showed an improved trend towards OS benefit with TAGRISSO compared to placebo in patients with unresectable, Stage III EGFRm NSCLC (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.40, 1.14, maturity 31%). Median OS was 58.8 months (95% CI 54.1, not calculable [NC]) in patients treated with TAGRISSO versus 54.1 months with placebo (95% CI 42.1, NC), despite 78% of patients on placebo receiving subsequent treatment with TAGRISSO upon progression. The trial will continue to assess OS as a key secondary endpoint at the final analysis.
TAGRISSO previously demonstrated a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS). These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU and China.
Safety results and discontinuation rates due to adverse events (AEs) were as expected and no new safety concerns were identified.
TAGRISSO plus savolitinib showed durable response rates in lung cancer patients with high levels of MET overexpression and/or amplification whose disease progressed on 1st-line TAGRISSO in SAVANNAH trial
Results from the SAVANNAH Phase II trial showed TAGRISSO plus savolitinib (300 mg twice-daily [BID]) demonstrated a clinically meaningful and durable objective response rate (ORR) in patients with EGFRm NSCLC with high levels of MET overexpression and/or amplification whose disease progressed on treatment with 1st-line TAGRISSO. Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cut-off.
TAGRISSO plus savolitinib demonstrated a confirmed ORR of 56% (95% CI 45-67%), with a median duration of response (DoR) of 7.1 months (95% CI 5.6-9.6). Median PFS (mPFS) was 7.4 months (95% CI 5.5-7.6).
Safety results and discontinuation rates due to AEs were consistent with the established profiles of each medicine and no new safety concerns were reported. In all patients treated with TAGRISSO plus savolitinib (300 mg BID), Grade 3 or higher AEs occurred in 57% of patients.
Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor (TKI) being jointly developed and commercialized by AstraZeneca and HUTCHMED. In 2023, TAGRISSO plus savolitinib received Fast Track designation from the Food and Drug Administration (FDA) in this setting.
TAGRISSO plus datopotamab deruxtecan-dlnk showed encouraging response rates in patients whose disease progressed on 1st-line TAGRISSO in ORCHARD trial
First results from the TAGRISSO plus datopotamab deruxtecan-dlnk module of the ORCHARD Phase II platform trial showed the combination demonstrated promising efficacy and manageable safety in patients with advanced EGFRm NSCLC whose disease progressed on treatment with TAGRISSO.
The module enrolled an all-comer population of patients with EGFRm NSCLC and evaluated two doses of datopotamab deruxtecan-dlnk (4 or 6 mg/kg) which, in combination with TAGRISSO, showed similar ORRs of 43% (80% CI 31-55%) and 36% (80% CI 25-49%), respectively. PFS and DoR results favored the 6 mg/kg dose with a mPFS of 11.7 months (95% CI 8.3, NC) and 64% of patients continuing to respond at 9 months versus a mPFS of 9.5 months (95% CI 7.2-9.8) and 15% of patients continuing to respond at 9 months on the 4 mg/kg dose.
The safety profile of TAGRISSO plus datopotamab deruxtecan-dlnk was consistent with the known safety profiles of each medicine and no new safety concerns were identified at either dose level. Grade 3 or higher treatment-related AEs occurred in 34% and 56% of patients receiving the 4 mg/kg or 6 mg/kg doses, respectively.
Datopotamab deruxtecan-dlnk is a specifically engineered TROP2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. The Companies are evaluating datopotamab deruxtecan-dlnk alone and with TAGRISSO as treatment for patients with advanced or metastatic EGFRm NSCLC in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.
New results for TAGRISSO plus chemotherapy in the 1st-line setting reinforce strong PFS benefit in FLAURA2 Phase III trial
An exploratory post-hoc analysis of the FLAURA2 Phase III trial assessed PFS by length of exposure to pemetrexed maintenance treatment in patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO with the addition of chemotherapy (pemetrexed plus cisplatin) followed by maintenance treatment with TAGRISSO and chemotherapy (pemetrexed) or TAGRISSO alone. Results showed an mPFS of more than two years regardless of length of pemetrexed maintenance exposure, with a trend associating longer PFS with longer pemetrexed treatment.
The safety profile of TAGRISSO plus chemotherapy was consistent with the established profiles of the individual medicines. Grade 3 or higher chemotherapy-related AEs were reported in 16% of patients who received maintenance treatment for 3 to less than 9 months, and 10% for patients who received maintenance for 9 or more months. Chemotherapy discontinuation rates due to AEs were 18% and 10%, respectively.
TAGRISSO plus chemotherapy previously demonstrated a statistically significant and clinically meaningful improvement in PFS. These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU, Japan and China. Previously presented OS data from the second interim analysis showed a favorable trend with the TAGRISSO plus chemotherapy arm (HR 0.75; 95% CI 0.57-0.97, maturity 41%), with consistent results across all prespecified subgroups. The trial will continue to assess OS as a key secondary endpoint.
IMPORTANT SAFETY INFORMATION
ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT):
For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis
INDICATIONS
Notes
NSCLC
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for about 80% of cases.2 Approximately 10 to 15% of patients with NSCLC in the US and Europe and 30 to 40% of patients in Asia have an EGFR mutation.3-5
While EGFR-TKIs have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.6-9
LAURA
LAURA is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with TAGRISSO 80 mg once-daily (QD) oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with TAGRISSO.
The trial enrolled 216 patients in more than 145 centers across more than 15 countries, including in the US, Europe, South America and Asia.
SAVANNAH
SAVANNAH is an ongoing randomized, global Phase II trial studying the efficacy of savolitinib added to TAGRISSO in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification whose disease progressed following treatment with TAGRISSO. Based on the original single-arm trial design, patients were treated with savolitinib 300 or 600 mg QD or 300 mg BID, in combination with oral TAGRISSO 80 mg QD. In 2022, a comparison of savolitinib 300 mg BID and TAGRISSO 80 mg QD to savolitinib 300 mg BID and placebo was added to the trial to evaluate contribution of components.
The trial has enrolled 369 patients to date in more than 80 centers globally, including in the US, Canada, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include PFS and DoR.
In August 2022, positive interim ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC).
The global SAFFRON Phase III trial will further assess the TAGRISSO plus savolitinib combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following treatment with TAGRISSO. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.
ORCHARD
ORCHARD (Osimertinib Resistance CoHorts, Addressing 1L Relapse Drivers) is an open-label, multi-center Phase II platform trial evaluating numerous TAGRISSO-based combinations as a treatment for patients with advanced EGFRm NSCLC whose disease has progressed on 1st-line TAGRISSO. The trial has 10 modules examining the efficacy, safety and tolerability of these targeted and non-targeted combination options, including TAGRISSO 80 mg QD plus datopotamab deruxtecan-dlnk given intravenously at 4 or 6 mg/kg on day one of every three-week cycle.
The trial has enrolled 247 patients to date in more than 40 centers globally, including in the US, Europe and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS and DoR.
FLAURA2
FLAURA2 is a randomized, open-label, multi-center, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO 80 mg QD oral tablets with the addition of chemotherapy (pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by TAGRISSO with pemetrexed maintenance every three weeks.
The trial enrolled 557 patients in more than 150 centers across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.
TAGRISSO
TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO (40 mg and 80 mg QD oral tablets) has been used to treat patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.
There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC. TAGRISSO is the only targeted therapy to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials.
As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.
Savolitinib
Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. MET is a tyrosine kinase receptor that has an essential role in normal cell development. Savolitinib blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is a known mechanism of acquired resistance to EGFR TKIs. The prevalence of MET depends on the sample type, detection method and assay cut-off used.
Savolitinib is approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations.
It is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers as a single treatment and in combination with other medicines.
Datopotamab deruxtecan-dlnk
Datopotamab deruxtecan-dlnk (datopotamab deruxtecan in rest of world) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan-dlnk is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan-dlnk is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datopotamab deruxtecan-dlnk (6 mg/kg) is approved in the US, Japan and Russia for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 Phase III trial.
In the US, a Biologics License Application for datopotamab deruxtecan-dlnk is under Priority Review for the treatment of adult patients with locally advanced or metastatic EGFRm NSCLC who have received prior systemic therapies, including an EGFR-directed therapy. Datopotamab deruxtecan-dlnk was also granted Breakthrough Therapy Designation by the FDA for this patient population.
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 gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan-dlnk in collaboration with Daiichi Sankyo; 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 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 catalyze 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.
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