Datopotamab deruxtecan granted Priority Review in the US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer
AstraZeneca and Daiichi Sankyo have received Priority Review from the FDA for datopotamab deruxtecan (Dato-DXd) in treating adult patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior therapies. The FDA decision is expected in Q3 2025.
The application is supported by data from multiple trials, including TROPION-Lung05, which showed a 42.7% objective response rate and a median duration of response of 7.0 months in previously treated patients. The drug previously received Breakthrough Therapy Designation for this indication.
If approved, datopotamab deruxtecan would become the first TROP2-directed antibody drug conjugate for lung cancer. The companies are currently conducting seven Phase III trials evaluating the drug alone and in combinations for NSCLC treatment.
AstraZeneca e Daiichi Sankyo hanno ricevuto la Revisione Prioritaria dalla FDA per datopotamab deruxtecan (Dato-DXd) nel trattamento di pazienti adulti con cancro ai polmoni non a piccole cellule (NSCLC) avanzato e mutato nell'EGFR, che hanno ricevuto precedenti terapie. La decisione della FDA è attesa per il terzo trimestre del 2025.
L'applicazione è sostenuta da dati provenienti da molteplici studi, tra cui il TROPION-Lung05, che ha mostrato un 42,7% di tasso di risposta obiettiva e una durata mediana della risposta di 7,0 mesi nei pazienti precedentemente trattati. Il farmaco ha ricevuto in precedenza la Designazione di Terapia Innovativa per questa indicazione.
Se approvato, datopotamab deruxtecan diventerebbe il primo farmaco anticorpale congiugato diretto a TROP2 per il cancro al polmone. Le aziende stanno attualmente conducendo sette studi di Fase III per valutare il farmaco da solo e in combinazione nel trattamento del NSCLC.
AstraZeneca y Daiichi Sankyo han recibido Revisión Prioritaria de la FDA para datopotamab deruxtecan (Dato-DXd) en el tratamiento de pacientes adultos con cáncer de pulmón de células no pequeñas (NSCLC) avanzado y mutado en EGFR que han recibido terapias previas. Se espera que la decisión de la FDA sea en el tercer trimestre de 2025.
La solicitud está respaldada por datos de múltiples ensayos, incluidos TROPION-Lung05, que mostró un 42.7% de tasa de respuesta objetiva y una duración mediana de respuesta de 7.0 meses en pacientes previamente tratados. El fármaco recibió anteriormente la designación de Terapia Innovadora para esta indicación.
Si se aprueba, datopotamab deruxtecan se convertiría en el primer fármaco anticuerpo conjugado dirigido a TROP2 para el cáncer de pulmón. Las empresas están llevando a cabo actualmente siete ensayos de Fase III para evaluar el fármaco solo y en combinaciones para el tratamiento del NSCLC.
AstraZeneca와 Daiichi Sankyo는 이전 치료를 받은 고급 EGFR 변이 비소세포 폐암(NSCLC) 성인 환자를 치료하기 위해 datopotamab deruxtecan (Dato-DXd)에 대해 FDA로부터 우선 검토를 받았습니다. FDA의 결정은 2025년 3분기에 예상됩니다.
이 신청서는 여러 시험에서 나온 데이터에 의해 지원되며, TROPION-Lung05를 포함하여, 이전에 치료받은 환자에서 42.7%의 객관적 반응률과 7.0개월의 평균 반응 지속 기간을 보였습니다. 이 약물은 이 적응증에 대해 이전에 혁신 치료 지정(Breakthrough Therapy Designation)을 받았습니다.
승인될 경우, datopotamab deruxtecan는 폐암 치료를 위한 최초의 TROP2 표적 항체 약물 접합체가 될 것입니다. 이 회사들은 현재 NSCLC 치료를 위해 약물을 단독 및 조합하여 평가하는 7개의 3상 시험을 수행하고 있습니다.
AstraZeneca et Daiichi Sankyo ont reçu une Révision Prioritaire de la FDA pour datopotamab deruxtecan (Dato-DXd) dans le traitement des patients adultes atteints d'un cancer du poumon non à petites cellules (NSCLC) avancé et muté à l'EGFR, qui ont déjà reçu des traitements antérieurs. La décision de la FDA est attendue au troisième trimestre 2025.
La demande est soutenue par des données provenant de plusieurs essais, y compris TROPION-Lung05, qui a montré un taux de réponse objective de 42,7 % et une durée médiane de réponse de 7,0 mois chez les patients précédemment traités. Le médicament a précédemment reçu la désignation de Thérapie Révolutionnaire pour cette indication.
Si approuvé, datopotamab deruxtecan deviendrait le premier médicament anticorps conjugué dirigé contre TROP2 pour le cancer du poumon. Les entreprises réalisent actuellement sept essais de phase III évaluant le médicament seul et en combinaison pour le traitement du NSCLC.
AstraZeneca und Daiichi Sankyo haben von der FDA eine priorisierte Überprüfung für datopotamab deruxtecan (Dato-DXd) zur Behandlung von erwachsenen Patienten mit fortgeschrittenem EGFR-mutiertem nicht-kleinzelligem Lungenkrebs (NSCLC), die zuvor behandelt wurden, erhalten. Die Entscheidung der FDA wird im 3. Quartal 2025 erwartet.
Der Antrag wird von Daten aus mehreren Studien unterstützt, einschließlich TROPION-Lung05, die eine 42,7% objektive Ansprechraten und eine mediane Ansprechdauer von 7,0 Monaten bei zuvor behandelten Patienten zeigte. Das Medikament erhielt zuvor die Bezeichnung als Durchbruchtherapie für diese Indikation.
Wenn es genehmigt wird, würde datopotamab deruxtecan das erste TROP2-richtete Antikörper-Wirkstoff-Konjugat für Lungenkrebs werden. Die Unternehmen führen derzeit sieben Phase-III-Studien durch, in denen das Medikament alleine und in Kombinationen zur NSCLC-Behandlung evaluiert wird.
- Received FDA Priority Review status, indicating potential significant improvements over available options
- Demonstrated 42.7% objective response rate in clinical trials
- Previously granted Breakthrough Therapy Designation
- Would be first TROP2-directed antibody drug conjugate approved for lung cancer
- FDA decision not expected until Q3 2025
- Median duration of response to 7.0 months
Insights
To put this in perspective: current second-line treatments typically show response rates of 20-30%. The 7.0-month median duration of response suggests meaningful clinical benefit for patients who have exhausted standard treatment options.
In simpler terms, this drug is showing promising results in helping lung cancer patients whose current treatments have stopped working, potentially offering them months of additional response to treatment.
The Priority Review status, combined with the previous Breakthrough Therapy Designation, suggests high confidence in the drug's potential and could accelerate market entry. If approved, datopotamab deruxtecan would be the first TROP2-directed ADC in lung cancer, potentially establishing a new standard of care in the second-line setting.
For investors, this represents a potential catalyst for both companies, with peak sales estimates likely to be revised upward if approved in Q3 2025.
Key differentiators include: 1) Targeting TROP2, which is broadly expressed in NSCLC tumors, 2) Demonstrated efficacy in a heavily pretreated population and 3) A manageable safety profile consistent with previous studies.
The ongoing combination studies with osimertinib could potentially expand the drug's utility into earlier treatment lines, representing additional upside potential. This comprehensive development approach suggests a well-planned strategy to maximize the drug's commercial potential across multiple NSCLC treatment settings.
Application based on TROPION-Lung05 trial and supported by data from TROPION-Lung01 and TROPION-PanTumor01 trials
Approval would mark the first for AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan in lung cancer
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 EGFRm NSCLC in the TROPION-Lung05 and TROPION-Lung01 trials presented at the European Society for Medical Oncology (ESMO)
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, recognize 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 osimertinib as treatment for patients with advanced or metastatic EGFRm nonsquamous NSCLC.
Notes
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
For patients with tumors 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 tumors.12 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.7,13
TROPION-Lung05
TROPION-Lung05 is a global, multicenter, 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 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 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
Primary results from TROPION-Lung05 were published in the Journal of Clinical Oncology in January 2025.
TROPION-Lung01
TROPION-Lung01 is a global, randomized, multicenter, 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
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.
About TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicenter Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumors 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, HR-positive, HER2-low or 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
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.
Datopotamab deruxtecan clinical development program
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 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 commercialize fam-trastuzumab deruxtecan-nxki in March 2019 and datopotamab deruxtecan in July 2020, except in
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 osimertinib and gefitinib; durvalumab and tremelimumab; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan 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.
About 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
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US-96963 Last Updated 1/25
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