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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Peter
Schmid
+44 (0)20 7882 8764
p.schmid@qmul.ac.uk
Dr
DIAMOND Coordinating team
-
-
bci-diamond@qmul.ac.uk
Locally advanced or metastatic PD-L1 negative, triple-negative breast cancer
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
This study is being carried out to see if datopotamab deruxtecan in combination with durvalumab is effective than datopotamab deruxtecan alone in treating PDL1-negative advanced or metastatic triple-negative breast cancer (TNBC). Breast cancer is the most common malignancy in women and the second most common cancer overall. The term TNBC is used to define tumours that do not express oestrogen receptors, progesterone receptors and HER2 receptors. TNBC comprises 10 -15% of all breast cancers. It remains the subtype with the poorest outcome and there is a significant need to develop new therapies for this group of patients, especially. Moreover, the PDL1-negative tumour has demonstrated no benefit from standard first-line treatment of chemotherapy plus immune checkpoint inhibitors. Datopotamab deruxtecan is an antibody drug conjugate (ADC) that targets tumour-associated calcium signal transducer 2, TROP2, a transmembrane protein that is highly expressed in various epithelial tumors, including breast cancer. Durvalumab is an immune checkpoint inhibitor and is expected to stimulate the patient’s antitumour immune response by binding to PD-L1 and shifting the balance toward an antitumour response. The preclinical and clinical evidence have suggested synergistic activity between antibody drug conjugate and immune checkpoint inhibitor.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
You may not be able to take part if:
1. Prior chemotherapy, immunotherapy (including durvalumab) or treatment with PARP inhibitors for advanced or metastatic breast cancer2. Prior treatment with immune checkpoint inhibitors (eg atezolizumab, pembrolizumab) or DNA topoisomerase I or TROP2- or HER2-targeting ADCs and TROP2 targeted therapy in the (neo)adjuvant setting within 6 months from the end of treatment and randomisation into this study3. Patients with prior allogeneic stem cell or solid organ transplantation.4. Patients must not have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent), or had oral or IV steroids for 14 days prior to the first dose of study drug5. Administration of a live vaccine within 30 days prior to the first dose of study drug. 6. Active or prior documented autoimmune or inflammatory disorders7. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, radiation pneumonitis, organizing pneumonia requiring steroids, or evidence of active pneumonitis on screening chest CT scan.8. Active infection requiring systemic therapy.9. History of HIV infection10. Known active hepatitis infection or hepatitis C. 11. Known history of active tuberculosis 12. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol.14. Concurrent treatment with other experimental drugs or participation in another clinical trial with therapeutic intent within 28 days prior to randomisation.15. Pregnant and lactating female patients.16. Major surgical procedure within 4 weeks prior to randomisation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.17. Malignancies other than breast cancer within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent)18. Severe infections within 28 days prior to randomisation in the study, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.19. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy 20. Uncontrolled intercurrent illness21. History of leptomeningeal carcinomatosis22. Has clinically significant corneal disease23. Has a history of severe hypersensitivity reactions to other monoclonal antibodies24. History of active primary immunodeficiency 25. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.26. Brain metastases or neoplastic spinal cord compression. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as two brain images, both of which are obtained after treatment of the brain metastases). These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression. In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its equivalent and anticonvulsants for at least 14 days prior to the start of treatment.27. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from three ECGs (within 15 minutes at 5 minutes apart).28. Patients who have received prior anti–PD-1, anti PD-L1 or anti CTLA-4
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Dr
Peter
Schmid
+44 (0)20 7882 8764
p.schmid@qmul.ac.uk
Dr
DIAMOND Coordinating team
-
-
bci-diamond@qmul.ac.uk
The study is sponsored by Queen Mary University of London and funded by AstraZeneca UK.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
