DATOPOTAMAB DERUXTECAN for Triple-negative breast cancer | Brain metastases

Inclusion criteria

• {"criterion_text":"- Histologically confirmed breast cancer\n- Triple-negative disease\n- Newly diagnosed untreated brain metastases or brain metastases progressing after prior local therapy\n- Measurable disease (RANO-BM criteria)\n- No indication for immediate local treatment\n- Accompanying type II leptomeningeal disease allowed (suspected LMD by clinical findings and neuroimaging)\n- KPS ≥70%, ECOG ≤2\n- Indication for systemic anti-cancer treatment\n- Prior exposure to PD-1, PD-L1 inhibitors\n- Life expectancy of at least 3 months\n- Age ≥18 years\n- Patient must be able to tolerate therapy\n- Adequate bone-marrow, liver and kidney function\n- Adequate treatment washout period before enrolment, defined as:\n- Major Surgery: ≥3 weeks\n- Radiation therapy to the chest: ≥4 weeks\n- Palliative radiation therapy to other areas: ≥2 weeks\n- Chemotherapy, small-molecule targeted agents: ≥3 weeks\n- Antibody-based treatment: ≥4 weeks (concurrent therapy with denosumab allowed)\n- Patient must be capable of understanding the purpose of the study and have given written informed consent\n- No prior treatment with sacituzumab Govitecan or other Trop2-directed ADCs"}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity to Dato-DXd or any of the drug components\n- Use of any investigational agent within 28 days prior to initiation of treatment\n- History of malignancies other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 3 years including contralateral breast cancer\n- Other anticancer therapy\n- Concomitant radiotherapy\n- A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs\n- Clinically significant cardiac d\n- Inadequate bone marrow function at baseline prior to study entry:\n- Inadequate kidney function\n- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) including active or uncontrolled infections with hepatitis B and C\n- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesse\n- Has a history of non-infectious ILD/pneumonitis that required steroids,\n- Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study\n- Patients with active opportunistic infections\n- Known human immunodeficiency virus (HIV) infection that is not well controlled.\n- Pregnant or lactating women. Women with childbearing potential must have a negative pregnancy test at screening\n- Women with childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Acceptable contraception methods included the application of an intrauterine device, barrier method or total abstinence\n- Male subjects unable or unwilling to use adequate contraception methods\n- Patients with known substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results\n- Patients requiring concomitant use of chronic systemic (IV or oral) corticosteroids at doses higher than 8 mg dexamethasone per day o\n- Patients with significant corneal disease\n- Prior treatment with sacituzumab Govitecan or other Trop2-directed ADCs"}

Primary endpoints

• {"endpoint_text":"- intracranial response rate at any timepoint as judged by best response during the study period (response measured according to RANO-BM criteria)","definition_or_measurement_approach":"Response measured according to RANO-BM criteria; best response during the study period as judged by investigators."}

Secondary endpoints

• {"endpoint_text":"- extracranial response rate (response measured according to RECIST 1.1), bicompartmental clinical benefit rate (CBR; CR+PR+SD ≥6 months; intracranial CBR measured by RANO-BM; extracranial CBR measured by RECIST 1.1), progression-free survival, overall survival","definition_or_measurement_approach":"Extracranial response measured by RECIST 1.1; intracranial CBR measured by RANO-BM; extracranial CBR defined as CR+PR+SD ≥6 months; PFS and OS as time-to-event outcomes (no further details provided)."}

Other endpoints

• {"endpoint_text":"- To evaluate tissue, blood and imaging biomarkers associated with response to Dato-DXd.","definition_or_measurement_approach":"Exploratory biomarker analyses on tissue, blood and imaging samples; no further measurement detail provided."}

Austria

Earliest CTIS Part Ii Submission Date

19-11-2024

Latest Decision Or Authorization Date

10-12-2024

Processing Time Days

21

Number Of Sites

1

Number Of Participants

20

Ireland

Earliest CTIS Part Ii Submission Date

07-01-2026

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

16

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Medical University Of Vienna

Organisation Type

Educational Institution

Country Of Registered Address

Austria