AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan reduced the risk of disease progression or death by 37%, providing a 2-month median PFS benefit, and was well tolerated in post-endocrine therapy setting

WILMINGTON, DE, USA I October 23, 2023 I Positive results from the pivotal TROPION-Breast01 Phase III trial showed that datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy.

These data will be shared today in the first of two late-breaking presentations for datopotamab deruxtecan in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain (LBA11).

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

In the dual primary endpoint analysis, datopotamab deruxtecan reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.52-0.76; p<0.001) as assessed by blinded independent central review (BICR). Median PFS was 6.9 months in patients treated with datopotamab deruxtecan versus 4.9 with chemotherapy. A consistent PFS benefit was observed across subgroups. Results also showed a confirmed objective response rate (ORR) of 36.4% in patients treated with datopotamab deruxtecan compared to an ORR of 22.9% with chemotherapy.

For the dual primary endpoint of overall survival (OS), interim results numerically favored datopotamab deruxtecan over chemotherapy (HR 0.84; 95% CI 0.62-1.14), however, results did not reach statistical significance at the time of this data cut-off. The trial is ongoing to assess OS.

Aditya Bardia, MD, MPH, Director of Breast Cancer Research, Mass General Cancer Center, Associate Professor of Medicine at Harvard Medical School and investigator in the trial, said: “Despite the initial benefit of endocrine therapy, most patients with HR-positive, HER2-low or negative metastatic breast cancer will eventually experience disease progression and require additional treatment with chemotherapy. In the TROPION-Breast01 trial, datopotamab deruxtecan reduced patients’ risk of disease progression or death by more than a third and overall had fewer treatment-related serious adverse events than standard chemotherapy, illustrating its potential to become a new standard of care in a treatment setting where there is a clinical unmet need.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “With these TROPION-Breast01 results, datopotamab deruxtecan has the potential to meaningfully improve treatment expectations for patients with HR-positive, HER2-low or negative metastatic breast cancer by offering them an effective and better tolerated treatment option after endocrine therapy and only one line of chemotherapy. We look forward to continuing discussions with regulatory authorities with the goal of bringing this TROP2-directed antibody drug conjugate to eligible patients as soon as possible.”

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “These statistically significant and clinically meaningful results from the TROPION-Breast01 trial support datopotamab deruxtecan as a new potential standard of care for patients with advanced HR-positive, HER2-low or negative breast cancer in the post-endocrine therapy setting. The results further validate the portability of Daiichi Sankyo’s DXd antibody drug conjugate technology to additional targets such as TROP2, and we look forward to potentially bringing our second antibody drug conjugate to patients with breast cancer.”

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 21% and 45% of patients in the datopotamab deruxtecan and chemotherapy arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (1%, 31%), stomatitis (6%, 3%), fatigue (2%, 2%) and anemia (1%, 2%). In the datopotamab deruxtecan arm, the all grade interstitial lung disease (ILD) rate was low (3%) and the majority of events were low grade. There was one Grade 5 ILD event adjudicated as drug-related by an independent committee. The primary cause of death in this case was attributed to disease progression by the treating investigator.

Summary of TROPION-Breast01 Efficacy Results

  Datopotamab deruxtecan
Investigator’s choice
chemotherapy (n=367)
PFS, as assessed by BICR
Median PFS (95% CI) 6.9 months (5.7-7.4) 4.9 months (4.2-5.5)
HR (95% CI) 0.63 (0.52-0.76)
p-value p<0.0001
PFS, as assessed by investigator
Median PFS 6.9 months 4.5 months
HR (95% CI) 0.64 (0.53-0.76)
HR (95% CI) i 0.84 (0.62-1.14)
Confirmed ORR ii, iii 36.4% 22.9%
CR rate 0.5% 0%
PR rate 35.9% 22.9%

CI, confidence interval; CR, complete response; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response
i With median follow-up of 9.7 months, OS data were not mature
ii As assessed by BICR
iii ORR is (complete response + partial response)

After endocrine therapy, the most common prior treatments for patients in the datopotamab deruxtecan and chemotherapy arms, respectively, included one (63%, 61%) to two (37%, 38%) lines of chemotherapy and CDK4/6 inhibitor inhibitors (82%, 78%). At the July 17, 2023 data cut-off, 93 patients remained on treatment with datopotamab deruxtecan and 39 remained on chemotherapy.

AstraZeneca and Daiichi Sankyo have two Phase III trials evaluating datopotamab deruxtecan in triple-negative breast cancer (TNBC). TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic TNBC who are not candidates for anti-PD1/PD-L1 therapy. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without durvalumab versus investigator’s choice of therapy in patients with Stage I-III TNBC with residual disease after neoadjuvant therapy.

HR-positive breast cancer
Breast cancer is the most common cancer in the world and a leading cause of cancer-related death.1 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.1

Breast cancer is considered HR-positive, HER2-low or negative when tumors test positive for estrogen and/or progesterone hormone receptors and negative or low for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,3 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2

Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.4,5 Approximately 30% of patients diagnosed with HR-positive, HER2-low or negative metastatic breast cancer are expected to live five years after their diagnosis.2

TROP2 is a protein broadly expressed in several solid tumors, including HR-positive, HER2-low or negative breast cancer.6 TROP2 expression is associated with increased tumor progression and poor survival in patients with breast cancer.6,7

TROPION-Breast01 is a global, randomized, multicenter, open-label Phase III trial evaluating the safety and efficacy of datopotamab deruxtecan (6.0 mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with inoperable or metastatic HR-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have previously progressed on or are not suitable for endocrine therapy per investigator assessment and have received at least one systemic therapy.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and OS. Key secondary endpoints include ORR, duration of response, investigator-assessed PFS, disease control rate and time to first subsequent therapy.

TROPION-Breast01 enrolled more than 700 patients at sites in Asia, Europe, North America, South America and Africa. For more information visit

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 lead 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 development program called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumors, including non-small cell lung cancer, TNBC and hormone receptor-positive, HER2-low or negative breast cancer. Beyond the TROPION program, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.

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 Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment.

With fam-trastuzumab deruxtecan-nxki, a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines fulvestrant and goserelin and aims to reshape the HR-positive space with next-generation SERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.

PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (known as MSD outside the US and Canada) continues to research olaparib in these settings and to explore its potential in earlier disease.

To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy durvalumab, capivasertib in combination with chemotherapy, and durvalumab in combination with other oncology medicines, including olaparib and fam-trastuzumab deruxtecan-nxki.

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.

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 Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit and follow the Company on social media @AstraZeneca.


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SOURCE: Daiichi Sankyo