A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) in combination with Durvalumab compared with Pembrolizumab in combination with Investigator’s Choice of Chemotherapy (Paclitaxel/Nab-paclitaxel/Gemcitabine+Carboplatin) in Patients with PDL1 positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer

Research summary

cases in 2020 globally (11.7% of all new cancers). Breast cancer is also the fifth most common cause of death from cancer, with an estimated 685000 deaths in 2020 (Sung et al 2021). Despite advances in the diagnosis and treatment of breast cancer, around 5% to 10% of women diagnosed with breast cancer have metastatic disease at the time of diagnosis, with a much higher percentage in low- and middle-income countries, and up to 30% of women with early-stage non-metastatic breast cancer will develop metastatic disease (O'Shaughnessy 2005; Cardoso et al 2018; OECD 2019). Triple-negative breast cancers (TNBCs) account for 10% to 20% of newly diagnosed breast cancers (Dixon-Douglas et al 2022) and tend to have an aggressive clinical course and poorer prognosis than other breast cancer subtypes due to higher histological grade and lack of actionable molecular targets. In these early phase studies, Dato-DXd as monotherapy and in combination with durvalumab has encouraging anti-tumour activity and a manageable safety profile in patients with TNBC. Given these encouraging preliminary safety and efficacy data, the current study is designed to investigate the efficacy and safety of Dato-DXd in combination with durvalumab compared with investigator’s choice of chemotherapy (ICC) (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) in combination with pembrolizumab in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.

Principal Investigator

Dr Mark Henry Tuthill

Contact us

Email: latephaseoncology@ouh.nhs.uk

IRAS number

1007219