Datopotamab Deruxtecan Granted Priority Review in the U.S. for Patients with Previously Treated Advanced EGFR-Mutated Non-Small Cell Lung Cancer
AstraZeneca (AZN) and Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd) has received Priority Review status from the FDA for treating adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior therapies. The FDA's decision date is set for July 12, 2025.
The application is supported by data from multiple clinical trials, including TROPION-Lung05 phase 2, TROPION-Lung01 phase 3, and TROPION-PanTumor01 phase 1. A pooled analysis presented at ESMO Asia 2024 showed clinically meaningful tumor response, with a safety profile consistent with previous reports.
Dato-DXd, a TROP2 directed antibody drug conjugate, could become the first of its kind approved for lung cancer. The drug is currently being evaluated in seven phase 3 trials, including combinations with osimertinib for EGFR-mutated nonsquamous NSCLC.
AstraZeneca (AZN) e il datopotamab deruxtecan (Dato-DXd) di Daiichi Sankyo hanno ricevuto lo status di Revisione Prioritaria dalla FDA per il trattamento di pazienti adulti con cancro polmonare non a piccole cellule (NSCLC) localmente avanzato o metastatico con mutazione dell'EGFR che hanno già ricevuto terapie precedenti. La data di decisione della FDA è prevista per il 12 luglio 2025.
L'applicazione è supportata da dati provenienti da vari studi clinici, inclusi i trial TROPION-Lung05 di fase 2, TROPION-Lung01 di fase 3 e TROPION-PanTumor01 di fase 1. Un'analisi combinata presentata all'ESMO Asia 2024 ha mostrato una risposta tumorale clinicamente significativa, con un profilo di sicurezza coerente con le segnalazioni precedenti.
Il Dato-DXd, un anticorpo monoclonale coniugato diretto verso TROP2, potrebbe diventare il primo del suo genere ad essere approvato per il cancro ai polmoni. Attualmente, il farmaco è in fase di valutazione in sette trial di fase 3, inclusi abbinamenti con osimertinib per NSCLC non squamoso mutato per EGFR.
AstraZeneca (AZN) y el datopotamab deruxtecan (Dato-DXd) de Daiichi Sankyo han recibido el estatus de Revisión Prioritaria por parte de la FDA para tratar a pacientes adultos con cáncer de pulmón no microcístico (NSCLC) localmente avanzado o metastásico con una mutación en EGFR que han recibido tratamientos previos. La fecha de decisión de la FDA está programada para el 12 de julio de 2025.
La solicitud se apoya en datos provenientes de múltiples ensayos clínicos, incluyendo TROPION-Lung05 fase 2, TROPION-Lung01 fase 3 y TROPION-PanTumor01 fase 1. Un análisis combinado presentado en ESMO Asia 2024 mostró una respuesta tumoral clínicamente significativa, con un perfil de seguridad consistente con informes anteriores.
El Dato-DXd, un conjugado de anticuerpo dirigido a TROP2, podría convertirse en el primero de su tipo aprobado para el cáncer de pulmón. Actualmente, el medicamento se está evaluando en siete ensayos de fase 3, incluyendo combinaciones con osimertinib para el NSCLC no escamoso mutado por EGFR.
AstraZeneca (AZN)와 Daiichi Sankyo의 datopotamab deruxtecan (Dato-DXd)이 선행 치료를 받은 국소 진행성 또는 전이성 EGFR 변이 비소세포 폐암 (NSCLC) 성인 환자의 치료를 위해 FDA로부터 우선 심사 상태를 받았습니다. FDA의 결정 날짜는 2025년 7월 12일로 예정되어 있습니다.
이 신청은 TROPION-Lung05 2상, TROPION-Lung01 3상 및 TROPION-PanTumor01 1상을 포함한 여러 임상 시험의 데이터를 기반으로 하고 있습니다. 2024년 ESMO 아시아에서 발표된 수치 집계 결과, 임상적으로 의미 있는 종양 반응을 보였으며, 이전 보고와 일치하는 안전성 프로필을 가지고 있었습니다.
Dato-DXd는 TROP2에 대한 항체 약물 결합체로 폐암 치료를 위해 승인될 수 있는 첫 번째 사례가 될 수 있습니다. 현재 이 약물은 EGFR 변이 비편평 NSCLC에 대한 osimertinib와의 조합을 포함해 7개의 3상 시험에서 평가되고 있습니다.
AstraZeneca (AZN) et le datopotamab deruxtecan (Dato-DXd) de Daiichi Sankyo ont reçu le statut de Revue Prioritaire de la FDA pour le traitement des patients adultes atteints de cancer du poumon non à petites cellules (NSCLC) localement avancé ou métastatique porteurs d'une mutation de EGFR ayant déjà reçu des thérapies antérieures. La date de décision de la FDA est fixée au 12 juillet 2025.
La demande est soutenue par des données provenant de plusieurs essais cliniques, y compris TROPION-Lung05 phase 2, TROPION-Lung01 phase 3 et TROPION-PanTumor01 phase 1. Une analyse combinée présentée à l'ESMO Asia 2024 a montré une réponse tumorale cliniquement significative, avec un profil de sécurité cohérent avec les rapports précédents.
Dato-DXd, un conjugué d'anticorps dirigé contre TROP2, pourrait devenir le premier de son genre approuvé pour le cancer du poumon. Le médicament est actuellement évalué dans sept essais de phase 3, y compris des combinaisons avec l'osimertinib pour le NSCLC non squameux muté par EGFR.
AstraZeneca (AZN) und das von Daiichi Sankyo entwickelte datopotamab deruxtecan (Dato-DXd) haben vom FDA den Status der Prioritätsprüfung für die Behandlung von erwachsenen Patienten mit lokal fortgeschrittenem oder metastasiertem EGFR-mutiertem nicht-kleinzelligem Lungenkrebs (NSCLC) erhalten, die bereits vorherige Therapien erhalten haben. Das Entscheidungsdatum der FDA ist auf den 12. Juli 2025 festgelegt.
Der Antrag wird durch Daten aus mehreren klinischen Studien unterstützt, einschließlich TROPION-Lung05 Phase 2, TROPION-Lung01 Phase 3 und TROPION-PanTumor01 Phase 1. Eine zusammengefasste Analyse, die auf der ESMO Asia 2024 präsentiert wurde, zeigte eine klinisch relevante Tumorantwort mit einem Sicherheitsprofil, das mit früheren Berichten übereinstimmt.
Dato-DXd, ein auf TROP2 gerichteter Antikörper-Wirkstoff-Konjugat, könnte der erste seiner Art sein, der für Lungenkrebs zugelassen wird. Das Medikament wird derzeit in sieben Phase-3-Studien untersucht, einschließlich Kombinationen mit Osimertinib für EGFR-mutierte nicht-squamous NSCLC.
- FDA granted Priority Review status, indicating potential significant improvements over available options
- Previously received Breakthrough Therapy Designation from FDA
- Clinical trials demonstrated meaningful tumor response in target patient population
- Could become first TROP2 directed antibody drug conjugate approved for lung cancer
- None.
Insights
The FDA's Priority Review acceptance for datopotamab deruxtecan (Dato-DXd) represents a significant milestone in the treatment landscape for EGFR-mutated NSCLC. The July 12, 2025 PDUFA date could potentially introduce the first TROP2-directed ADC for lung cancer, addressing a critical unmet need in the
The drug's mechanism as a TROP2-directed ADC is particularly noteworthy, as it offers a novel approach for patients who have developed resistance to existing EGFR-TKIs. The pooled analysis data presented at ESMO Asia 2024 showing clinically meaningful tumor response, combined with the previously granted Breakthrough Therapy Designation, suggests a strong efficacy profile that could position this therapy as a valuable second-line treatment option.
The extensive clinical development program, including seven phase 3 trials, demonstrates AstraZeneca's commitment to maximizing the drug's potential across multiple treatment settings. The combination studies with osimertinib could potentially establish new treatment paradigms in EGFR-mutated NSCLC.
This regulatory milestone carries substantial commercial implications for AstraZeneca. The NSCLC market for EGFR-mutated patients represents a multi-billion dollar opportunity, with current second-line treatments showing efficacy. A successful launch could generate peak annual sales estimates of
The collaboration with Daiichi Sankyo follows AstraZeneca's successful strategy with Enhertu, another ADC that has become a blockbuster drug. This Priority Review status typically correlates with a
The NSCLC therapeutic landscape is experiencing a paradigm shift toward precision medicine and Dato-DXd's potential approval could reshape market dynamics. Current second-line treatment options for EGFR-mutated NSCLC patients have shown durability, creating a substantial market opportunity. The drug's development program, particularly the combination studies with osimertinib, indicates a strategic approach to maximize market penetration.
Competition in this space is intensifying, but Dato-DXd's novel mechanism of action and potential first-to-market status as a TROP2-directed ADC in lung cancer could provide AstraZeneca with a significant competitive advantage. Early adoption patterns among oncologists suggest strong interest in ADC technologies, potentially leading to rapid market uptake if approved.
- Application based on TROPION-Lung05 phase 2 trial and supported by data from TROPION-Lung01 phase 3 and TROPION-PanTumor01 phase 1 trials
Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and AstraZeneca.
The
The BLA and BTD are based on data from the TROPION-Lung05 phase 2 trial and supported by data from the TROPION-Lung01 phase 3 trial. In addition, the BLA is supported by the TROPION-PanTumor01 phase 1 trial. In a pooled analysis of patients with previously treated advanced or metastatic EGFR-mutated NSCLC in the TROPION-Lung05 and TROPION-Lung01 trials presented at the European Society for Medical Oncology (ESMO)
“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,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “If approved, datopotamab deruxtecan could become the first TROP2 directed antibody drug conjugate for lung cancer, providing a promising option for patients.”
“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,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “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.”
Daiichi Sankyo and AstraZeneca are evaluating datopotamab deruxtecan alone and in novel combinations as treatment for patients with NSCLC in seven phase 3 trials including the TROPION-Lung14 and TROPION-Lung15 trials of datopotamab deruxtecan alone and with osimertinib, AstraZeneca’s EGFR tyrosine kinase inhibitor (TKI), as treatment for patients with advanced or metastatic EGFR-mutated nonsquamous NSCLC.
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 of TROPION-Lung05 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
Primary results from TROPION-Lung05 were published in the Journal of Clinical Oncology in January 2025.
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
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 TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicenter phase 1 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 (6 mg/kg). The dose expansion part of TROPION-PanTumor01 enrolled several different cohorts including patients with NSCLC, triple negative breast cancer (TNBC), 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 also are being evaluated.
TROPION-PanTumor01 enrolled approximately 900 patients in
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
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.
Datopotamab deruxtecan is approved in
About the 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, TNBC 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
About the 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 (Dato-DXd), 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,
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.
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.
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References
1 World Health Organization. Global Cancer Observatory: Lung. Accessed January 2025.
2 American Cancer Society. Key Statistics for Lung Cancer. Accessed January 2025.
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 January 2025.
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.
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FAQ
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