Phase II Study of Dato-DXd in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases (TUXEDO-2)

Medical University of Vienna

Status and phase

Enrolling

Phase 2

Conditions

Breast Cancer Stage IV

Treatments

Drug: Datopotamab deruxtecan

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05866432

TUXEDO-2

Details and patient eligibility

About

Datopotamab-deruxtecan in triple-negative breast cancer patients with newly diagnosed or progressing brain metastases.

Full description

Datopotamab-deruxtecan will be administered at a dose of 6.0 mg/kg body weight i.v. on day

1 once every three weeks in triple-negative breast cancer patients with newly diagnosed or progressing brain metastases. Response rate by RANO-BM criteria is definied as primary endpoint.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed breast cancer
Triple-negative disease as defined by immunohistochemistry (IHC) and/or c-erb-B2 gene amplification status. For the definition of hormone-receptor negative disease, a cut-off of <10% tumour cells with positive staining of oestrogen- and progresteron-receptors is required
Newly diagnosed untreated brain metastases or brain metastases progressing after prior local therapy
Measurable disease (RANO-BM criteria)
No indication for immediate local treatment
Accompanying type II leptomeningeal disease allowed (suspected LMD by clinical findings and neuroimaging)
KPS ≥70%, ECOG ≤2 Indication for systemic anti-cancer treatment
Prior exposure to PD-1, PD-L1 inhibitors and TROP-2 targeted agents allowed
Life expectancy of at least 3 months
Age ≥18 years
Patient must be able to tolerate therapy
Adequate bone-marrow, liver and kidney function
Adequate treatment washout period before enrolment, defined as:
Major Surgery: ≥3 weeks
Radiation therapy to the chest: ≥4 weeks
Palliative radiation therapy to other areas: ≥2 weeks
Chemotherapy, small-molecule targeted agents: ≥3 weeks
Antibody-based treatment: ≥4 weeks (concurrent therapy with denosumab allowed)
Patient must be capable of understanding the purpose of the study and have given written informed consent

Exclusion criteria

Known hypersensitivity to Dato-DXd or any of the drug components
Use of any investigational agent within 28 days prior to initiation of treatment
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
Other anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, retinoid, or anti-cancer hormonal treatment with the exception of osteoprotective therapies such as denosumab or bisphosphonates
Concomitant radiotherapy
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
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), left ventricular ejection fraction <50%, arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities, and long QT syndrome (QTc interval >470 ms)
Inadequate bone marrow function at baseline prior to study entry
Inadequate kidney function
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 including active or uncontrolled infections with hepatitis B and C
Participants with known hepatitis B and C are eligible if they:
1. Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies
2. Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis
3. Are HBsAg- and anti-HBc+ (i.e., those who have cleared HBV after infection) and meet conditions i-iii below:
4. Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions 1-3 below:
5. HBV DNA viral load <2000 IU/mL
6. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT <3 × ULN, which are not attributable to HBV infection
7. Start or maintain antiviral treatment
Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
Has a history of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
Patients with active opportunistic infections
Known human immunodeficiency virus (HIV) infection that is not well controlled
Pregnant or lactating women
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.
Male subjects unable or unwilling to use adequate contraception methods
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
Patients requiring concomitant use of chronic systemic (IV or oral) corticosteroids at doses higher than 8 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events; (inhaled steroids or intra articular steroid injections are permitted in this study)
Patients with significant corneal disease