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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05866432

Studienbeginn:
Juli 2023

Letztes Update:
19.10.2023

Wirkstoff:
Datopotamab Deruxtecan

Indikation (Clinical Trials):
Breast Neoplasms, Brain Neoplasms, Triple Negative Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Medical University of Vienna

Collaborator:
Daiichi Sankyo, Inc.

Studienleiter

Rupert Rupert, MD
Principal Investigator
Medical University Vienna

Kontakt

Rupert Rupert, MD
Kontakt:
Phone: +43140400
Phone (ext.): 44450
E-Mail: rupert.bartsch@meduniwien.ac.at» Kontaktdaten anzeigen

Marika Rosner
Kontakt:
Phone: +43140400
Phone (ext.): 44450
E-Mail: marika.rosner@meduniwien.ac.at» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

AKH Universitaetsklinikum Vienna, Department f. Internal medicine I, oncology
1090 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Rupert Bartsch, MD
Phone: +43140400
Phone (ext.): 44450
E-Mail: rupert.bartsch@meduniwien.ac.at» Ansprechpartner anzeigen

Studien-Informationen

Detailed 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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Intracranial response rate to datopotamab-deruxtecan (Time Frame - From date of inclusion until the date of firstdocumented progression or date of death from any cause or treatmentdiscontinuation from any other reason, whichever came first, assessedup to 36 months]):
Measured according to RANO-BM criteria

Secondary outcome:

1. Entracranial response rate to datopotamab-deruxtecan (Time Frame - From date of inclusion until the date of firstdocumented progression or date of death from any cause or treatmentdiscontinuation from any other reason, whichever came first, assessedup to 36 months]):
Measured according to RECIST 14.1 criteria

2. Progression-free survival (Time Frame - From date of inclusion until the date of firstdocumented progression or date of death from any cause or treatmentdiscontinuation from any other reason, whichever came first, assessedup to 36 months]):
Time from inclusion until progression

3. Overall Survival (Time Frame - From date of inclusion until the date of firstdocumented progression or date of death from any cause or treatmentdiscontinuation from any other reason, whichever came first, assessedup to 36 months]):
Time from inclusion until progression

4. Safety & tolerability of datopotamab-deruxtecan in terms of haematologic and non-haematologic side effect (Time Frame - From date of inclusion until the date of firstdocumented progression or date of death from any cause or treatmentdiscontinuation from any other reason, whichever came first, assessedup to 36 months]):
Assessment of clinical adverse events & laboratory parameters

Geprüfte Regime

Datopotamab deruxtecan (S-1062a):
Will be given until PD or withdraw

Quelle: ClinicalTrials.gov

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