Datopotamab Deruxtecan

First and only EGFR inhibitor and targeted treatment approved in the EU in unresectable NSCLC Approval based on LAURA Phase III trial results which showed Tagrisso extended median progression-free survival to more than three years LONDON, UK I December 23, 2024 I AstraZeneca’s Tagrisso (osimertinib) has been approved in the European Union (EU) for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor ( EGFR ) exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy (CRT). The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the LAURA Phase III trial, which were published in The New England Journal of Medicine . In the trial, Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio 0.16; 95% confidence interval 0.10-0.24; p<0.001) as assessed by blinded independent central review. Median progression-free survival (PFS) was 39.1 months in patients treated with Tagrisso versus 5.6 months for placebo. Overall survival (OS) results remain immature, and the trial is continuing to assess OS as a secondary endpoint. Each year in Europe, there are more than 450,000 people diagnosed with lung cancer, and approximately 80-85% have NSCLC. 1-3 Among those with NSCLC in Europe, about 10-15% have tumours with an EGFR mutation. 4-6 Manuel Cobo, MD, Specialist Physician of the Medical Oncology Service at the Carlos Haya University Hospital, Malaga, Spain, and investigator for the trial, said: “Today’s approval marks a major breakthrough for patients in the EU with unresectable, EGFR -mutated non-small cell lung cancer, delivering the first targeted treatment in this setting. Osimertinib reduced the risk of disease progression or death by an unprecedented 84 per cent in the LAURA trial, setting a new benchmark for outcomes and underscoring the importance of testing for EGFR mutations upon diagnosis.” Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “ Tagrisso is now the first and only EGFR inhibitor and targeted treatment approved in the EU for locally advanced, unresectable lung cancer, providing a new standard of care to patients who have historically experienced early progression after chemoradiation therapy. The powerful results from the LAURA trial show Tagrisso improves outcomes for patients in the unresectable setting, reinforces the importance of timely EGFR testing and solidifies Tagrisso as the backbone therapy in EGFR -mutated non-small cell lung cancer.” The safety and tolerability of Tagrisso in the LAURA trial was consistent with its established profile and no new safety concerns were identified. This is the fifth major approval for Tagrisso based on the LAURA trial following recent approvals in the US, Switzerland, South Korea and Australia. Regulatory applications are also currently under review in China, Japan and several other countries. Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include 1st-line treatment of patients with locally advanced or metastatic EGFR m NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFR m NSCLC. Tagrisso is also approved in combination with chemotherapy in the US, China and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFR m NSCLC. Notes Lung cancer Each year, an estimated 2.4 million people are diagnosed with lung cancer globally. 7 Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. 7 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer. 2,3 The majority of all NSCLC patients are diagnosed with advanced disease. 8 ​Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFR m NSCLC. 4-6 Patients with EGFR m NSCLC are particularly sensitive to treatment with an EGFR -tyrosine kinase inhibitor ( EGFR -TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells. 9 LAURA LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFR m NSCLC whose disease has not progressed following definitive platinum‑based CRT. Patients were treated with Tagrisso 80mg once-daily 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 centres across more than 15 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 (40mg and 80mg once-daily 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 EGFR m NSCLC. There is an extensive body of evidence supporting the use of Tagrisso as standard of care in EGFR m NSCLC. Tagrisso improved patient outcomes in early-stage disease in the ADAURA Phase III trial , Stage III, unresectable disease in the LAURA Phase III trial , late-stage disease in the FLAURA Phase III trial , and with chemotherapy in the FLAURA2 Phase III trial . As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib as well as other potential new medicines. 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 (trastuzumab deruxtecan) and 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 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 . References SOURCE: AstraZeneca

TOKYO & BASKING RIDGE, N.J.--( BUSINESS WIRE )--Datopotamab deruxtecan (Dato-DXd) has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR-mutated) non-small cell lung cancer (NSCLC) with disease progression on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat serious conditions and address significant unmet medical needs. The medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines. The FDA granted this BTD based on data from the TROPION-Lung05 phase 2 trial with supporting data from the TROPION-Lung01 phase 3 trial. Results from a pooled analysis of patients with previously treated EGFR-mutated NSCLC in these studies were presented this month at the European Society of Medical Oncology (ESMO) Asia 2024 Congress. This is the first BTD for datopotamab deruxtecan and the twelfth BTD across Daiichi Sankyo’s oncology pipeline. “ The Breakthrough Therapy Designation granted by the FDA underscores the significant unmet need for new treatments for patients with previously treated EGFR-mutated non-small cell lung cancer who have experienced disease progression,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “ Datopotamab deruxtecan has the potential to play an important role in improving outcomes and we look forward to working closely with the FDA to bring this medicine to patients as quickly as possible.” “ This Breakthrough Therapy Designation reinforces datopotamab deruxtecan as a promising potential therapy for patients with EGFR-mutated lung cancer who continue to face significant unmet needs following disease progression on or after initial treatments,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “ We are proud to have long supported patients with EGFR-mutated lung cancer and look forward to the possibility of bringing another innovative treatment option to this community.” Daiichi Sankyo and AstraZeneca recently announced the submission of a new Biologics License Application for accelerated approval in the U.S. for datopotamab deruxtecan for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior systemic therapies, including an EGFR-directed therapy. About TROPION-Lung05 TROPION-Lung05 is a global, multicenter, single-arm, open-label phase 2 trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on at least one TKI (with or without other systemic therapies) and on or after one regimen of platinum-based chemotherapy. Patients receiving up to four prior lines of treatment with tumors with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial. The primary trial endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary efficacy endpoints include duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety. TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information visit ClinicalTrials.gov . About TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . Primary PFS results and interim OS results from TROPION-Lung01 were presented at the 2023 ESMO (#ESMO23) Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology in September 2024. About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 80% of cases. 2 Approximately 10% to 15% of patients with NSCLC in the U.S. and Europe, and 30% to 40% of patients in Asia have an EGFR mutation. 3,4 The majority of EGFR mutations occur in tumors of nonsquamous histology. 5 For patients with tumors that have an EGFR mutation, the established first-line treatment in the metastatic setting is an EGFR TKI. 6 While EGFR TKIs have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive subsequent therapies, such as chemotherapy. 7,8,9,10 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 11 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 6,12 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan 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 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. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 low or negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and 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 datopotamab deruxtecan. About the DXd ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . _______________________________ References 1 World Health Organization. Global Cancer Observatory: Lung. Accessed December 2024. 2 American Cancer Society. Key Statistics for Lung Cancer . Accessed December 2024. 3 Szumera-Ciećkiewicz A, et al. Int J Clin Exp Pathol . 2013;6(12): 2800-2812. 4 Ellison G, et al. J Clin Pathol . 2013;66(2):79-89. 5 Prabhakar C. Translational Lung Cancer Research . 2015; 4(2), 110-118. 6 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed December 2024. 7 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 8 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 9 Morgillo F, et al. ESMO Open . 2016;1:e000060. 10 Han B, et al. Onco Targets Ther . 2018;11:2121-9. 11 Mito R, et al. Pathol Int . 2020;70(5):287-294. 12 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7): 881-895.