Daiichi Sankyo Company, Limited announced that the first patient was dosed in the global TROPION-Breast01 phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (Dato-DXd), a TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca, in patients with hormone receptor (HR) positive, human epidermal growth factor 2 receptor (HER2) negative inoperable or metastatic breast cancer previously treated with chemotherapy.

Breast cancer is the most common cancer worldwide with more than two million cases diagnosed in 2020, resulting in nearly 685,000 deaths globally. Approximately 70% of all breast cancers are considered HR positive, HER2 negative. For patients with HR positive, HER2 negative metastatic breast cancer that progresses on or is not suitable for hormone therapy-based regimens, current standard of care is single-agent chemotherapy, which demonstrates diminishing efficacy with each subsequent line of treatment.

“There are no TROP2 directed therapies currently approved for HR positive, HER2 negative breast cancer and we are encouraged by the emerging clinical profile of datopotamab deruxtecan in patients with breast cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president, global head, oncology development, oncology R&D, Daiichi Sankyo. “TROPION-Breast01 is the first pivotal trial of datopotamab deruxtecan in breast cancer and the third pivotal study in our clinical development programme, underscoring our efforts to accelerate development of this TROP2 directed ADC in breast and lung cancer.”
“Most patients with HR positive, HER2 negative metastatic breast cancer will inevitably progress on available treatments, including hormonal therapy and standard of care chemotherapy. In this setting, the unmet need is high, and new therapeutic approaches are necessary to delay disease progression and extend survival,” said Cristian Massacesi, MD, chief medical officer and oncology chief development officer, AstraZeneca. “The TROPION-Breast01 trial will evaluate whether datopotamab deruxtecan may be a more effective treatment than chemotherapy for patients with previously treated HR positive, HER2 negative advanced breast cancer previously treated with one to two lines of chemotherapy.”

TROPION-Breast01 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6 mg/kg) compared with investigator’s choice of chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with inoperable or metastatic HR positive, HER2 negative breast cancer (per ASCO/CAP guidelines, on local laboratory results) who have progressed on or were not suitable for endocrine therapy and previously treated with one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting.
The dual primary endpoints of TROPION-Breast01 are progression-free survival (PFS) assessed by blinded independent central review and overall survival. Secondary endpoints include PFS assessed by investigator, objective response rate, duration of response, disease control rate, and patient reported outcomes, as well as safety and pharmacokinetics.

TROPION-Breast01 will enroll approximately 700 patients at sites in Africa, Asia, Europe, North America and South America.

Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide. More than two million cases of breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein overexpressed in several types of solid tumors, including breast cancer. TROP2 expression has been detected in a wide range of breast cancer subtypes, including the HR positive, HER2 negative subtype.

Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of three 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 IgG13 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.