Datopotamab Deruxtecan Recommended for Approval in the EU by CHMP for Patients with Previously Treated Metastatic HR Positive, HER2 Negative Breast Cancer
Datopotamab deruxtecan (Dato-DXd) has received a positive CHMP recommendation for EU approval in treating adult patients with unresectable or metastatic HR positive, HER2 negative breast cancer who have previously received endocrine therapy and chemotherapy in advanced settings.
The recommendation is based on the TROPION-Breast01 phase 3 trial results, which showed that Dato-DXd reduced the risk of disease progression or death by 37% compared to standard chemotherapy. The median progression-free survival was 6.9 months for Dato-DXd versus 4.9 months for chemotherapy. The objective response rate was 36% for Dato-DXd compared to 23% for chemotherapy.
The drug demonstrated a favorable safety profile with 21% of patients experiencing Grade 3 or higher treatment-related adverse events compared to 45% in the chemotherapy arm. The drug is already approved in Japan and the U.S., with additional regulatory submissions under review in China and other regions.
Datopotamab deruxtecan (Dato-DXd) ha ricevuto una raccomandazione positiva dal CHMP per l'approvazione nell'UE per il trattamento di pazienti adulti con cancro al seno HR positivo e HER2 negativo in stadio avanzato, non resecabile o metastatico che hanno precedentemente ricevuto terapia endocrina e chemioterapia.
La raccomandazione si basa sui risultati del fase 3 dello studio TROPION-Breast01, che ha mostrato che Dato-DXd ha ridotto il rischio di progressione della malattia o morte del 37% rispetto alla chemioterapia standard. La sopravvivenza mediana senza progressione è stata di 6,9 mesi per Dato-DXd contro 4,9 mesi per la chemioterapia. Il tasso di risposta obiettiva è stato del 36% per Dato-DXd rispetto al 23% per la chemioterapia.
Il farmaco ha dimostrato un profilo di sicurezza favorevole, con 21% dei pazienti che hanno sperimentato eventi avversi correlati al trattamento di Grado 3 o superiore rispetto al 45% nel braccio chemioterapico. Il farmaco è già approvato in Giappone e negli Stati Uniti, con ulteriori invii normativi in fase di revisione in Cina e altre regioni.
Datopotamab deruxtecan (Dato-DXd) ha recibido una recomendación positiva del CHMP para su aprobación en la UE para el tratamiento de pacientes adultos con cáncer de mama HR positivo y HER2 negativo no resecable o metastásico que han recibido previamente terapia endocrina y quimioterapia en etapas avanzadas.
La recomendación se basa en los resultados del ensayo de fase 3 TROPION-Breast01, que mostró que Dato-DXd redujo el riesgo de progresión de la enfermedad o muerte en un 37% en comparación con la quimioterapia estándar. La mediana de supervivencia libre de progresión fue de 6,9 meses para Dato-DXd frente a 4,9 meses para la quimioterapia. La tasa de respuesta objetiva fue del 36% para Dato-DXd comparado con el 23% para la quimioterapia.
El medicamento demostró un perfil de seguridad favorable, con un 21% de pacientes experimentando eventos adversos relacionados con el tratamiento de Grado 3 o superior en comparación con el 45% en el grupo de quimioterapia. El medicamento ya está aprobado en Japón y EE. UU., con presentaciones regulatorias adicionales en revisión en China y otras regiones.
다토포타맙 데룩스테칸 (Dato-DXd)이 절제 불가능하거나 전이성인 HR 양성, HER2 음성 유방암 치료를 위해 EU 승인을 위한 CHMP의 긍정적인 권고를 받았습니다. 이 환자군은 이전에 내분비 요법과 고급 화학요법을 받은 성인 환자들입니다.
이 권고는 TROPION-Breast01 임상 3상 시험 결과에 기반하며, Dato-DXd는 표준 화학요법에 비해 질병 진행이나 사망 위험을 37% 줄인 것으로 나타났습니다. Dato-DXd의 중간 무진행 생존기간은 6.9개월로, 화학요법의 4.9개월보다 길었습니다. Dato-DXd의 객관적 반응률은 36%로, 화학요법의 23%에 비해 높았습니다.
이 약물은 안전성 프로필이 우수하게 나타났으며, 21%의 환자가 화학요법 그룹의 45%에 비해 3등급 이상의 치료 관련 부작용을 경험했습니다. 이 약물은 이미 일본과 미국에서 승인받았으며, 중국 및 기타 지역에서도 추가 규제 신청이 검토 중입니다.
Datopotamab deruxtecan (Dato-DXd) a reçu une recommandation positive du CHMP pour son approbation dans l'UE pour le traitement des patients adultes atteints de cancer du sein HR positif et HER2 négatif, non résécable ou métastatique, qui ont précédemment reçu une thérapie endocrine et une chimiothérapie dans des contextes avancés.
La recommandation est basée sur les résultats de l'
Le médicament a montré un profil de sécurité favorable, avec 21% des patients présentant des effets indésirables liés au traitement de Grade 3 ou supérieur contre 45% dans le groupe chimiothérapie. Le médicament est déjà approuvé au Japon et aux États-Unis, avec d'autres soumissions réglementaires en cours d'examen en Chine et dans d'autres régions.
Datopotamab Deruxtecan (Dato-DXd) hat eine positive Empfehlung des CHMP für die EU-Zulassung zur Behandlung erwachsener Patienten mit unresektablem oder metastasiertem HR-positivem, HER2-negativem Brustkrebs erhalten, die zuvor eine endokrine Therapie und Chemotherapie in fortgeschrittenen Stadien erhalten haben.
Die Empfehlung basiert auf den Ergebnissen der TROPION-Breast01 Phase-3-Studie, die zeigte, dass Dato-DXd das Risiko eines Krankheitsfortschritts oder Todes um 37% im Vergleich zur Standardchemotherapie reduzierte. Die mediane progressionsfreie Überlebenszeit betrug 6,9 Monate für Dato-DXd im Vergleich zu 4,9 Monaten für die Chemotherapie. Die objektive Ansprechrate lag bei 36% für Dato-DXd im Vergleich zu 23% für die Chemotherapie.
Das Medikament wies ein günstiges Sicherheitsprofil auf, wobei 21% der Patienten Grad-3- oder schwerwiegende behandlungsbedingte Nebenwirkungen erlebten, verglichen mit 45% in der Chemotherapie-Gruppe. Das Medikament ist bereits in Japan und den USA zugelassen, und weitere regulatorische Einreichungen befinden sich in Prüfung in China und anderen Regionen.
- 37% reduction in risk of disease progression or death compared to chemotherapy
- Higher objective response rate of 36% vs 23% for chemotherapy
- Better safety profile with fewer Grade 3+ adverse events (21% vs 45%)
- Already secured approvals in major markets (US and Japan)
- Longer progression-free survival of 6.9 months vs 4.9 months for chemotherapy
- One grade 5 ILD (interstitial lung disease) event reported as drug-related
- duration of response at 6.7 months
- 3% rate of interstitial lung disease reported as adverse event
Insights
The CHMP's positive recommendation for datopotamab deruxtecan marks a pivotal milestone for AstraZeneca's oncology portfolio expansion in the EU market. The drug's demonstrated 37% reduction in disease progression risk represents a significant clinical advantage in the treatment of HR positive, HER2 negative metastatic breast cancer, a condition with historically treatment options.
The commercial implications are substantial, considering that this breast cancer subtype represents approximately 70% of all breast cancer cases. The drug's superior efficacy profile, with a 36% objective response rate versus 23% for chemotherapy, coupled with a notably better safety profile (21% vs 45% grade 3+ adverse events), positions it favorably for rapid market adoption.
Several key differentiators strengthen its market position:
- Improved progression-free survival of 6.9 months vs 4.9 months
- Lower neutropenia rates of 1% vs 31% compared to chemotherapy
- Manageable safety profile with only 3% ILD rate
The recent approvals in the U.S. and Japan, combined with pending reviews in China and other regions, indicate strong momentum for global market penetration. This expansion could significantly impact AstraZeneca's oncology revenue stream, particularly given the high unmet need in this patient population where only one-third survive beyond five years after diagnosis.
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Recommendation based on TROPION-Breast01 results showing Daiichi Sankyo and AstraZeneca’s datopotamab deruxtecan reduced risk of disease progression or death by
37% versus chemotherapy -
Datopotamab deruxtecan approved in the
U.S. andJapan for same patient population
Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE:45680) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the TROPION-Breast01 phase 3 trial published in the Journal of Clinical Oncology. The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU.
In TROPION-Breast01, datopotamab deruxtecan significantly reduced the risk of disease progression or death by
Datopotamab deruxtecan demonstrated a favorable safety profile over chemotherapy with no new safety concerns identified. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in
“Disease progression after endocrine and initial chemotherapy is common in patients with metastatic HR positive, HER2 negative breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “This positive recommendation by the CHMP for datopotamab deruxtecan, which follows recent approvals in the
“Only one in three patients live more than five years after a metastatic HR positive, HER2 negative breast cancer diagnosis, underscoring the urgent need for additional effective therapies,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “Today’s recommendation for datopotamab deruxtecan brings us closer to offering these patients in the EU a new and needed alternative to conventional chemotherapy.”
Datopotamab deruxtecan is approved in
About TROPION-Breast01
TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of intravenous datopotamab deruxtecan (6 mg/kg) once per 21-day cycle versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one prior line of chemotherapy for unresectable or metastatic disease.
Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive a subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. The PFS data and additional results for key secondary endpoints of TROPION-Breast01 were published in the Journal of Clinical Oncology.
TROPION-Breast01 enrolled 732 patients in
About Hormone Receptor Positive, HER2 Negative Breast Cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than 500,000 breast cancer cases were diagnosed in
Approximately
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 non-small cell lung cancer, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes eight 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, 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.
References
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1 Bray F, et al. CA Cancer J Clin. 2024; 10.3322/caac.21834.
2 Globocan 2022.
3 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed January 2025.
4 Manohar P, et al. Cancer Biol Med. 2022 Feb 15; 19(2):202–212.
5 Cortes J, et al. Lancet. 2011;377:914-923.
6 Yuan P, et al. Eur J Cancer. 2019;112:57-65.
7 Jerusalem G, et al. JAMA Oncol. 2018;4(10):1367–1374.
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Source: Daiichi Sankyo
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