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First Phase III results in breast cancer for
and
Plans for global regulatory submissions underway
Positive high-level results from the TROPION-Breast01 Phase III trial showed datopotamab 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.
A trend in improvement for the dual primary endpoint of overall survival (OS) was observed for datopotamab deruxtecan versus chemotherapy. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS.
The safety profile of datopotamab deruxtecan was consistent with previous clinical trials in breast cancer with no new safety signals identified. All grade interstitial lung disease rates were low.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by
More than two million people worldwide are diagnosed with breast cancer each year.1 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.1,2 Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.3,4 TROP2 is a protein broadly expressed in HR-positive, HER2-low or negative breast cancer.5,6
The data will be presented at a forthcoming medical meeting and shared with health authorities.
Notes
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 tumours test positive for oestrogen and/or progesterone hormone receptors and negative or low for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,7 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 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 tumours, including HR positive, HER2-low or negative breast cancer.5 TROP2 expression is associated with increased tumour progression and poor survival in patients with breast cancer.5,6
TROPION-Breast01
TROPION-Breast01 is global, randomised, multicentre, open-label Phase III 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 previously progressed on or are not suitable for endocrine therapy per investigator assessment.
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
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using
A comprehensive development programme is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumours, including non-small cell lung cancer, triple-negative breast cancer and hormone receptor-positive, HER2-low or negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials.
Driven by a growing understanding of breast cancer biology,
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC,
In HR-positive breast cancer,
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer,
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
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References
1. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
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3. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.
4. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities.
5. Goldenberg D, et al. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9(48): 28989-29006.
6. Vidula N, et al. Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer. Breast Cancer Res Treat. 2022 Aug;194(3):569-575.
7. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014;852748.
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