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The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. 1 The Prescription Drug User Fee Act date, the FDA action date for its regulatory decision, is anticipated during the third quarter of 2025. Datopotamab deruxtecan was previously granted Breakthrough Therapy Designation (BTD) by the FDA for this patient population. The BLA and BTD are based on data from the TROPION-Lung05 Phase II trial and supported by data from the TROPION-Lung01 Phase III trial. In addition, the BLA is supported by data from the TROPION-PanTumor01 Phase I trial. In a pooled analysis of patients with previously treated advanced or metastatic EGFR m NSCLC in the TROPION-Lung05 and TROPION-Lung01 trials presented at the European Society for Medical Oncology (ESMO) Asia 2024 Congress, datopotamab deruxtecan demonstrated a confirmed objective response rate (ORR) of 42.7% (95% confidence interval [CI] 33.6-52.2) as assessed by blinded independent central review (BICR) and a median duration of response (DoR) of 7.0 months (95% CI 4.2-9.8). The safety profile of datopotamab deruxtecan was consistent with previous reports from the TROPION-Lung05 and TROPION-Lung01 trials, with no new safety concerns identified. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Acquired resistance to front-line therapies and, ultimately, disease progression are unfortunate realities for most patients with advanced EGFR -mutated non-small cell lung cancer. This Priority Review, and the previously granted Breakthrough Therapy Designation, recognise the potential for datopotamab deruxtecan to provide a much-needed option to patients whose disease has become resistant to current treatments.” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “Treating advanced EGFR -mutated non-small cell lung cancer presents a significant challenge due to the limited efficacy of available treatments once the disease has progressed following front-line therapies, including the use of an EGFR -tyrosine kinase inhibitor. If approved, datopotamab deruxtecan could become the first TROP2-directed antibody drug conjugate for lung cancer, providing a promising option for patients.” Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo. AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and in novel combinations as treatment for patients with NSCLC in seven Phase III trials including the TROPION-Lung14 and TROPION-Lung15 trials of datopotamab deruxtecan alone and with Tagrisso (osimertinib) as treatment for patients with advanced or metastatic EGFR m nonsquamous NSCLC. Advanced non-small cell lung cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 2 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 80% of cases. 3 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. 4,5 The majority of EGFR mutations occur in tumours of nonsquamous histology. 6 For patients with tumours that have an EGFR mutation, the established 1st-line treatment in the metastatic setting is an EGFR -TKI. 7 While EGFR -TKIs have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive subsequent therapies, such as chemotherapy. 8-11 TROP2 is a protein broadly expressed in the majority of NSCLC tumours. 12 There is currently no TROP2-directed ADC approved for the treatment of lung cancer. 7,13 TROPION-Lung05 TROPION-Lung05 is a global, multicentre, single-arm, open-label Phase II 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 tumours with one or more genomic alterations including EGFR , ALK , ROS1 , NTRK , BRAF , RET or MET were eligible for the trial. The primary endpoint of TROPION-Lung05 is ORR as assessed by BICR. Secondary efficacy endpoints include DoR, disease control rate (DCR), clinical benefit rate (CBR), 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. Primary results from TROPION-Lung05 were published in the Journal of Clinical Oncology in January 2025. TROPION-Lung01 TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III 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 results from TROPION-Lung01, as presented at the ESMO 2023 Congress, showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS over docetaxel. OS results were presented at the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology in September 2024. TROPION-PanTumor01 TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with NSCLC to assess the safety and tolerability of datopotamab deruxtecan to determine the recommended dose for expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01 enrolled several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), hormone receptor (HR)-positive, HER2-negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration resistant prostate and esophageal cancer. Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, TTR, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints are also being evaluated. TROPION-PanTumor01 enrolled approximately 900 patients in Asia and North America. For more information visit ClinicalTrials.gov. 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 programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised 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 is approved in Japan under the brand name Datroway for the treatment of adult patients with unresectable or recurrent HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer after prior chemotherapy based on the results of the TROPION-Breast01 trial. Datopotamab deruxtecan is an investigational medicine in all countries outside of Japan. Datopotamab deruxtecan clinical development programme A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, TNBC and HR-positive, HER2-negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu (trastuzumab deruxtecan) 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. 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 (durvalumab) and Imjudo (tremelimumab); Enhertu 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. Datopotamab deruxtecan FDA Approval History Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

LONDON--( BUSINESS WIRE )-- Ellipses Pharma Limited ( “ Ellipses”), a global drug development company focused on accelerating the development of cancer treatments through an innovative drug development model, announced today it has inaugurated the first large-scale Phase 1/2 oncology clinical study of its kind in the United Arab Emirates, marking a significant milestone in the region ’ s healthcare landscape. Following approval by the UAE regulators and the Ministry and Department of Health, this study will be conducted initially at two major healthcare centres in Abu Dhabi - the Cleveland Clinic and Tawam Hospital. The inclusion of a third study centre is pending. Patient recruitment has commenced. The trial will focus on Ellipses' next generation selective RET inhibitor (SRI), EP0031/A400, a potential treatment of RET-altered tumours, most prevalent in non-small cell lung cancer and thyroid cancer. Professor Sir Christopher Evans, OBE, Executive Chairman, Ellipses, said: “Our mission to find outstanding potential cancer treatments and develop them at pace has been made possible in a very large part by the unwavering support we have had from our investors in Abu Dhabi who embraced the Ellipses model and vision from its early stages. “This tremendous commitment has led us to the point where our achievements can be brought to bear for the potential benefit of patients in UAE. In many ways, we can now bring hope and an innovative therapy to people in the UAE and also enable healthcare professionals to collaborate and share research. This trial is the first of many trials we hope to conduct in the region.” Sir Chris is one of several global life sciences and healthcare experts on the Advisory Board of M42, the pioneering Abu Dhabi based tech enabled company, which is supporting the Ellipses initiative, and serves on the board of directors of the Emirates Drug Establishment. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to EP0031/A400 in November 2023 and in March of this year granted it Fast Track Designation, which facilitates the expedited development and review of new drugs intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Professor Tobias Arkenau, Global Head of Drug Development and Chief Medical Officer, Ellipses commented: “The opening of the EP0031/A400 trial in the UAE is a very exciting initiative. Through trials carried out to date, our belief has been reinforced that EP0031/A400 has the potential to be a transformational next generation RET inhibitor - in particular for patients with RET-positive NSCLC and thyroid cancers, which remain a progressive and fatal condition for hundreds of thousands of patients worldwide.” About EP0031/A400 EP0031/A400 is being developed jointly by Ellipses in a global clinical phase 1/2 trial under the name EP0031 (NCT05443126) and Kelun Biotech (6990.HK) in China under the name A400 (NCT05265091). Modular Phase 1 studies have been conducted in the US, Europe and China and registrational Phase 2 trials in China and US, Europe and UAE are ongoing. In March 2021, Kelun-Biotech granted Ellipses an exclusive license for EP0031/A400 in certain territories including the US and Europe, with Kelun-Biotech retaining certain rights in Greater China and certain Asian countries. An Investigational New Drug Application (IND) application for EP0031/A400 was approved by China’s National Medicinal Products Administration in June 2021 and a registrational Phase 2 trial is ongoing in China. In June 2022, the U.S. Food and Drug Administration approved the EP0031/A400 Phase 1/2 study IND application in the US. About RET altered malignancies Activating RET mutations and rearrangements have been identified as actionable drivers of oncogenesis in numerous tumour types and are most prevalent in non-small cell lung and thyroid cancer. It is estimated that RET mutations and rearrangements may be responsible for ~2% of all solid tumours. After the successful development of first generation SRIs and an increasing understanding of escape mechanisms to these agents, there is an unmet need to develop new treatments that can address acquired resistance, including the development of next-generation SRIs. About Ellipses Pharma Limited Ellipses is a global drug development company based in London, focused on accelerating the development of cancer treatments through an innovative drug development model that combines unbiased vetting to de-risk initial asset selection with an uninterrupted funding flow to minimise the time it takes to advance lead products through clinical trials and reach patients. www.ellipses.life About Kelun-Biotech Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 1 project has been approved for marketing, 3 projects are in the NDA stage, and more than 10 projects are in the clinical stage. The company has established one of the world’s leading proprietary ADC platforms, OptiDC™, and has 1 ADC project approved for marketing, 1 ADC project in NDA stage, and multiple ADC or novel ADC projects in clinical or preclinical research stage. For more information, please visit https://kelun-biotech.com/ .

On December 16, Innovent Biologics and Eli Lilly announced a collaboration agreement for the non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, pirtobrutinib, in mainland China. Under this agreement, Innovent Biologics will handle the import, sales, promotion, and distribution, while Eli Lilly will manage R&D and post-market medical affairs. On October 29, Eli Lilly’s pirtobrutinib received approval from the National Medical Products Administration (NMPA) for treating relapsed or refractory mantle cell lymphoma (MCL) in adults who have previously received BTK inhibitor treatments. Currently, the domestic market has five approved BTK inhibitors, including ibrutinib, zanubrutinib, ocatabrutinib, and acabrutinib. Sanofi’s Tolebrutinib and Rilzabrutinib are in Phase III clinical trials, while CT-1530 from Shouyao Holdings is in Phase II. The robust development of BTK inhibitors indicates potential market changes. BTK inhibitors work by targeting the BCR signaling pathway, binding to BTK, inhibiting its phosphorylation, and inducing apoptosis, effectively managing B-cell malignancies. Before BTK inhibitors, lymphoma treatments were limited to chemotherapy, anti-CD20 antibodies, and radiotherapy. Ibrutinib, the first BTK inhibitor, revolutionized B-cell cancer treatment since its 2013 debut and was approved in China in 2017. However, sales of ibrutinib have slowed due to competition from similar drugs. Zanubrutinib, developed by BeiGene, reached $1.297 billion in global sales in 2023, marking the first domestic drug to achieve such success, but it now faces increasing competition. Pirtobrutinib, as the first and only non-covalent BTK inhibitor, intensifies competition in this niche market. It shows potential to overcome resistance to covalent BTK inhibitors and offers a new option for relapsed/refractory MCL patients. To highlight its efficacy, Eli Lilly conducted a head-to-head study in the BRUIN MCL-321 trial. By 2030, pirtobrutinib is projected to capture 60% of the chronic lymphocytic leukemia market, equating to $3 billion in annual sales. With advancing technology and new drug development, the BTK market is expanding rapidly. According to Frost & Sullivan, the global BTK market could reach $20 billion by 2025 and $26.1 billion by 2030. In China, the market size is expected to reach RMB 13.1 billion by 2025 and RMB 22.5 billion by 2030. The growing BTK market has attracted numerous pharmaceutical companies. At least 20 BTK inhibitors are in clinical trials domestically, with Shouyao Holdings, Hengrui Medicine, and Hezheng Pharmaceutical leading the way. Ibrutinib’s core patent will expire on December 28, 2026, and at least 10 companies are preparing generics. This will lead to fierce competition among original drugs, domestic innovations, and generics. BeiGene’s zanubrutinib remains a key product, but new competitors like pirtobrutinib pose challenges. The success of pirtobrutinib in China’s market is worth monitoring. Originally developed by Redx Pharma and acquired by Loxo Oncology, pirtobrutinib was purchased by Eli Lilly for $8 billion in 2019. In March 2022, Innovent Biologics secured Chinese commercialization rights for pirtobrutinib with an initial payment of $45 million. The partnership between Innovent Biologics and Eli Lilly began in 2015 and has expanded through multiple projects. Despite setbacks like sintilimab’s rejection by the U.S. FDA in 2022, their collaboration continues with other initiatives. Their 2019 cooperation on IBI362, a dual GLP-1R and GCGR agonist, is in Phase II/III trials for Type 2 diabetes and weight loss. In March 2022, Eli Lilly’s ramucirumab was approved in China, granting Innovent Biologics exclusive commercialization rights. Additionally, they collaborate on selpercatinib, a RET inhibitor for gene fusion tumors. The cooperation and competition between domestic and multinational pharmaceutical companies are becoming a norm. This model offers a win-win strategy for navigating the global market.