Treatment for triple-negative breast cancer with brain metastases

Phase II Study of Datopotamab-Deruxtecan (Dato-DXd; DS-1026a) in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases

This study is testing a new treatment called datopotamab-deruxtecan for people with triple-negative breast cancer that has spread to the brain to see if it helps them feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Medical University of Vienna (Academic / other)
• Drugs / interventions: denosumab, Chemotherapy, immunotherapy, Radiation, Datopotamab
• Locations: 1 site (Vienna, State of Vienna)
• Trial ID: NCT05866432 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of datopotamab-deruxtecan in patients with triple-negative breast cancer who have newly diagnosed or progressing brain metastases. Participants will receive the treatment intravenously at a dose of 6.0 mg/kg every three weeks. The primary endpoint is the response rate assessed by RANO-BM criteria. The study aims to provide a new therapeutic option for this challenging condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed triple-negative breast cancer and newly diagnosed or progressing brain metastases.

Not a fit: Patients with stable brain metastases who do not require systemic anti-cancer treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with triple-negative breast cancer and brain metastases.

How similar studies have performed: While similar studies have explored treatments for brain metastases in breast cancer, this specific approach with datopotamab-deruxtecan is novel.

Eligibility criteria

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

Where this trial is running

Vienna, State of Vienna

• AKH Universitaetsklinikum Vienna, Department f. Internal medicine I, oncology — Vienna, State of Vienna, Austria (Recruiting)

Study contacts

• Principal investigator: Rupert Rupert, MD — Medical University Vienna
• Study coordinator: Rupert Rupert, MD

Conditions Breast Cancer Stage IV