Datopotamab Deruxtecan Granted Breakthrough Therapy Designation in U.S. for Patients with Previously Treated Advanced EGFR-Mutated Non-Small Cell Lung Cancer
Datopotamab deruxtecan (Dato-DXd) has received Breakthrough Therapy Designation (BTD) from the FDA for treating adult patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) who have experienced disease progression after EGFR tyrosine kinase inhibitor and platinum-based chemotherapy treatments.
The BTD, which aims to accelerate development and regulatory review of promising medicines, was granted based on data from the TROPION-Lung05 phase 2 trial and supporting data from the TROPION-Lung01 phase 3 trial. This marks the first BTD for datopotamab deruxtecan and the twelfth BTD across Daiichi Sankyo's oncology pipeline.
Daiichi Sankyo and AstraZeneca have submitted a new Biologics License Application for accelerated approval in the U.S. for this treatment.
Datopotamab deruxtecan (Dato-DXd) ha ricevuto la Designazione di Terapia Innovativa (BTD) dalla FDA per il trattamento di pazienti adulti con cancro ai polmoni non a piccole cellule (NSCLC) con mutazione EGFR in stadio avanzato che hanno subito una progressione della malattia dopo trattamenti con inibitori della tirosina chinasi EGFR e chemioterapia a base di platino.
La BTD, che ha l'obiettivo di accelerare lo sviluppo e la revisione normativa di farmaci promettenti, è stata concessa sulla base di dati provenienti dallo studio di fase 2 TROPION-Lung05 e dati di supporto dallo studio di fase 3 TROPION-Lung01. Questo segna la prima BTD per datopotamab deruxtecan e la dodicesima BTD nell'ambito della pipeline oncologica di Daiichi Sankyo.
Daiichi Sankyo e AstraZeneca hanno presentato una nuova Domanda di Licenza Biologica per approvazione accelerata negli Stati Uniti per questo trattamento.
Datopotamab deruxtecan (Dato-DXd) ha recibido la Designación de Terapia Innovadora (BTD) de la FDA para el tratamiento de pacientes adultos con cáncer de pulmón no microcítico (NSCLC) con mutación en el EGFR y que han experimentado progresión de la enfermedad tras tratamientos con inhibidores de la tirosina quinasa del EGFR y quimioterapia basada en platino.
La BTD, que tiene como objetivo acelerar el desarrollo y la revisión regulatoria de medicamentos prometedores, fue otorgada con base en datos del ensayo de fase 2 TROPION-Lung05 y datos de apoyo del ensayo de fase 3 TROPION-Lung01. Esto marca la primera BTD para datopotamab deruxtecan y la duodécima BTD en la cartera oncológica de Daiichi Sankyo.
Daiichi Sankyo y AstraZeneca han presentado una nueva Solicitud de Licencia Biológica para aprobación acelerada en EE. UU. para este tratamiento.
다토포타맙 데룩시탄 (Dato-DXd)은 FDA로부터 EGFR 변이 비소세포 폐암 (NSCLC)이 진행된 성인 환자의 치료를 위한 혁신 치료 지정(BTD)을 받았습니다. 이 환자들은 EGFR 티로신 키나제 억제제와 플래티넘 기반 화학요법 치료 후에 질병이 진행되었습니다.
BTD는 유망한 약물의 개발 및 규제 검토를 가속화하기 위해 마련된 것으로, TROPION-Lung05 2상 시험과 TROPION-Lung01 3상 시험의 지원 데이터를 기반으로 승인되었습니다. 이는 다토포타맙 데룩시탄에 대한 첫 번째 BTD이자 다이이치 산쿄의 항암제 파이프라인에서의 12번째 BTD입니다.
다이이치 산쿄와 아스트라제네카는 이 치료에 대해 미국에서의 신속 승인을 위한 새로운 생물학적 제제 허가 신청서를 제출했습니다.
Datopotamab deruxtecan (Dato-DXd) a reçu la désignation de thérapie innovante (BTD) de la FDA pour traiter les patients adultes atteints de cancer du poumon non à petites cellules (NSCLC) muté par l'EGFR et ayant connu une progression de la maladie après des traitements par inhibiteurs de la tyrosine kinase de l'EGFR et chimiothérapie à base de platine.
La BTD, qui vise à accélérer le développement et l'examen réglementaire des médicaments prometteurs, a été accordée sur la base de données de l'
Daiichi Sankyo et AstraZeneca ont soumis une nouvelle demande de licence biologique pour une approbation accélérée aux États-Unis pour ce traitement.
Datopotamab Deruxtecan (Dato-DXd) hat von der FDA die Auszeichnung als Durchbruchtherapie (BTD) für die Behandlung von erwachsenen Patienten mit fortgeschrittenem EGFR-mutiertem nicht-kleinzelligem Lungenkrebs (NSCLC) erhalten, die nach einer Behandlung mit EGFR-Tyrosinkinase-Inhibitoren und einer platinbasierten Chemotherapie eine Krankheitsprogression erlebt haben.
Die BTD, die darauf abzielt, die Entwicklung und die regulatorische Überprüfung vielversprechender Medikamente zu beschleunigen, wurde auf der Grundlage von Daten aus der TROPION-Lung05 Phase-2-Studie und unterstützenden Daten aus der TROPION-Lung01 Phase-3-Studie gewährt. Dies markiert die erste BTD für Datopotamab Deruxtecan und die zwölfte BTD im Onkologie-Portfolio von Daiichi Sankyo.
Daiichi Sankyo und AstraZeneca haben einen neuen Antrag auf beschleunigte Zulassung in den USA für diese Behandlung eingereicht.
- Received FDA Breakthrough Therapy Designation, potentially accelerating regulatory review and development
- Submission of Biologics License Application for accelerated approval in the U.S.
- Addresses significant unmet medical need in EGFR-mutated NSCLC treatment
- None.
Insights
The FDA's Breakthrough Therapy Designation for datopotamab deruxtecan represents a significant milestone in addressing a critical unmet need in EGFR-mutated NSCLC treatment. This designation, based on promising data from two clinical trials, could substantially accelerate the drug's path to market approval.
The therapeutic landscape for EGFR-mutated NSCLC has been challenging, particularly for patients who progress after standard treatments. Dato-DXd's novel TROP2-directed antibody-drug conjugate mechanism offers a potentially powerful new approach. The concurrent submission of a Biologics License Application for accelerated approval further strengthens the near-term commercial prospects.
The development carries substantial market implications for both AstraZeneca and Daiichi Sankyo, potentially establishing a new standard of care in this specific NSCLC segment. Success in this indication could lead to expanded applications and significant revenue potential in the
This regulatory milestone significantly enhances AstraZeneca's oncology portfolio value proposition. The BTD status not only accelerates the potential market entry but also validates the commercial viability of their strategic collaboration with Daiichi Sankyo.
The NSCLC market represents a substantial revenue opportunity, with the EGFR-mutated segment alone estimated to be worth several billion dollars annually. A successful launch could generate peak annual sales exceeding
This development strengthens AstraZeneca's competitive position in oncology, complementing their existing EGFR-targeted portfolio. The accelerated regulatory pathway could provide a first-mover advantage in this specific indication, potentially capturing significant market share before competing therapies emerge.
- First Breakthrough Therapy Designation for Daiichi Sankyo and AstraZeneca’s datopotamab deruxtecan based on TROPION-Lung05 phase 2 trial and supported by data from TROPION-Lung01 phase 3 trial
- Twelfth Breakthrough Therapy Designation granted by FDA across Daiichi Sankyo’s oncology pipeline
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
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)
“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
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
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 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.
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
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,
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.
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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.
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FAQ
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