Positive topline results from the TROPION-Breast01 phase 3 trial showed datASHamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of 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. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca. Data for the dual primary endpoint of overall survival (OS) were not mature at this interim analysis and the trial will continue as planned to assess OS.
The safety profile of datopotamab deruxte can was consistent with previous clinical trials in breast cancer with no new safety signals identified. All grade interstitial lung disease rates were low. More than two million people worldwide are diagnosed with breast cancer each year.
HR positive, HER2 low ornegative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases. Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options. TROP2 is a protein broadly expressed in HR positive, HER2 low and negative breast cancer.
Detailed results from the TROPION-Breast01 trial will be presented at an upcoming medical meeting and shared with regulatory authorities. Daiichi Sankyo and AstraZeneca have two additional phase 3 trials evaluating datopotamab deruxtecan in breast cancer. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for anti-PDL1 therapy.
TROPION-Breast03 is evaluating datopotamab deruxtecan with and without durvalumab versus investigator?s choice of therapyin patients with stage I-III TNBC with residual disease after neoadjuvant therapy. TROPION-Breast01 is global, randomized, multicenter, open-label phase 3 trial evaluating the safety and efficacy of datopotamab deruxtecan 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 progressed on or are not suitable for endocrine therapy per investigator assessment and at least one systemic therapy. The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review (BICR) and OS.
Key secondary endpoints include objective response rate, 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. 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.
Breast cancer is considered HR positive, HER2 low or negative when tumors test positive for estrogen and/or progesterone hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-). HR positive, HER2 low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases. Approximately 30% of patients diagnosed with HR positive, HER2 low or negative metastatic breast cancer are expected to live five years after their diagnosis.
TROP2 is a protein broadly expressed in several solid tumors, including HR positive, HER2 low or negative breast cancer. TROP2 expression is associated with increased tumor progression and poor survival in patients with breast cancer.