Phase II Study of daTopotamab-derUXtecan (Dato-DXd; DS-1026a) in triple-negative brEast cancer patients with newly Diagnosed or prOgressing brain metastases

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 May 2023 → ongoing

Decision date (initial)

2024-12-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518819-19-00

EudraCT number

2022-003203-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate the ability of Dato-DXd to induce objective CNS responses in patients with TNBC and newly diagnosed or progressive brain metastases.

Secondary objectives 1

1. To evaluate the activity of Dato-DXd on extracranial disease; to evaluate progression-free-survival (PFS) and overall survival (OS) in patients with active TNBC BM treated with Dato-DXd; and to evaluate safety and tolerability of Dato-DXd in a patient population of patients with active TNBC brain metastases; to evaluate QoL and neurocognitive functioning of study participants on Dato-DXd. Exploratory Objectives To evaluate tissue, blood and imaging biomarkers associated with response to Dato-DXd.

Conditions and MedDRA coding

triple negative breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. • Histologically confirmed breast cancer • Triple-negative disease • 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 • 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
2. • No prior treatment with sacituzumab Govitecan or other Trop2-directed ADCs

Exclusion criteria 2

1. • 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 • 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 d • 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 per investigator assessment) including active or uncontrolled infections with hepatitis B and C • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesse • Has a history of non-infectious ILD/pneumonitis that required steroids, • 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 must have a negative pregnancy test at screening • 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 • 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 o • Patients with significant corneal disease
2. • Prior treatment with sacituzumab Govitecan or other Trop2-directed ADCs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. intracranial response rate at any timepoint as judged by best response during the study period (response measured according to RANO-BM criteria)

Secondary endpoints 1

1. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Medicine I, Division of Oncology

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Medicine I, Division of Oncology

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications