Trastuzumab Deruxtecan in First-Line HER2-Positive Metastatic Breast Cancer With Proactive Toxicity Management

NCT07371585 | Recruiting Phase 2

• 2 other identifiers: SOLTI-24022025-521805-41-00
• Study Type: interventional
• Target: 300
• Locations: 3 countries
• Sites: 27

Brief Summary

This is an open-label, single arm, non-randomized, multicenter, phase 2 study assessing the efficacy and safety of T-DXd as first-line treatment in HER2-positive advanced/metastatic BC patients (N=300). The study integrates digital health tools for proactive toxicity management and potentially facilitate early detection of ILD/pneumonitis.

Conditions

Breast Cancer Stage IV

Keywords

Trastuzumab deruxtecan; digital health tools; first line; proactive toxicity management

Outcome Measures

Primary Outcomes (2)

• Efficacy of T-DXd as a first-line therapy - TFST

  Time to first subsequent anti-cancer therapy (TFST) is defined as the time from the date of first dose of the study treatment to the date of i) first subsequent anti-cancer therapy after disease progression or discontinuation of maintenance treatment (in patients who discontinued due to treatment-related toxicities), or ii) death from any cause, whichever occurs first

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled

• Health-related quality of life

  Time to 10% physical functioning deterioration, based on the EORTC QLQ-C30 Physical Functioning scale. Values range from 0 to 100. Higher scores mean a better outcome.

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdrawal of consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled.

Secondary Outcomes (13)

• Adverse events (safety)

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled

• Percentage of any acute or delayed nausea and vomiting

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled

• Unplanned healthcare utilization

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled

• Efficacy of T-DXd as a first-line therapy - PFS

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled

• Efficacy of T-DXd as a first-line therapy - ORR

  From date of enrollment until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 60 months after the first patient enrolled

Study Arms (1)

T-DXd + pertuzumab + digital health tools

EXPERIMENTAL

Trastuzumab Deruxtecan (T-DXd) in combination with pertuzumab, together with the use of digital health tools

Device: Digital Health Tools; Drug: T-DXd; Drug: Pertuzumab

Interventions

T-DXd DRUG

T-DXd at 5.4 mg/kg will be administered as IV infusion q3w.

Also known as: Trastuzumab deruxtecan + Pertuzumab, Pertuzumab

T-DXd + pertuzumab + digital health tools

Digital Health Tools DEVICE

Patients will be followed via digital health tools for proactive toxicity management, which consist of one mobile app and two devices: (1) CANKADO/Resilience app (depending on the country and site) accessed through the patient's phone; (2) A pulse oximeter that together with the digital health mobile app will allow self-tracking of vital parameters such as oxygen saturation and heart rate, potentially facilitating early ILD detection; and (3) A smartwatch to collect patient granular data. All three digital health tools/items are CE-marked medical devices, where relevant, used exclusively within their approved intended purpose, and not subject to any investigation of safety or performance within this study.

Also known as: CANKADO, Resilience, Pulse oximeter, Smartwatch

T-DXd + pertuzumab + digital health tools

Pertuzumab DRUG

Pertuzumab will be administered at a loading dose of 840 mg on Day 1 of Cycle 1, followed by 420 mg in subsequent cycles, administered as IV q3w.

T-DXd + pertuzumab + digital health tools

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand the nature of the study and to voluntarily provide written informed consent prior to any trial-specific screening procedures and has sufficient cognitive capacity to comply with study requirements, including the use of digital health tools and devices.
• Male/female patients who are at least 18 years of age on the day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Histologically or cytologically locally confirmed HR+/HER2+ or HR-/HER2+ BC with evidence of locally advanced disease, not amenable to resection or radiation therapy with curative intent, or metastatic disease:
• HER2-positivity confirmed in a tumor sample obtained in the metastatic setting, defined as either IHC 3+ or in situ hybridization positive (ISH+) by local laboratory assessment as per the most recent American Society of Clinical Oncology (ASCO)-College of American Pathologists Guideline (CAP) guideline. The most recent test result prior screening period will be used to confirm eligibility.
• Documented HR (ER and/or PR) positivity or negativity, confirmed by local laboratory assessment in a tumor sample obtained in the metastatic setting. ER and/or PR positivity is defined as \>1% of cells expressing HR via IHC analysis as per most recent ASCO-CAP guideline. The most recent test result prior screening period will be used to confirm eligibility.
• No prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). Participants who have received chemotherapy or HER2-targeted therapy in the neoadjuvant or adjuvant setting at any time are eligible.
• Note: Patients that received an antibody-drug conjugate containing an exatecan derivative (topoisomerase I inhibitor) in the adjuvant setting, must have a disease-free interval of ≥12 months since the last dose.
• Evaluable disease as defined by RECIST v1.1.
• Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
• Adequate FFPE tumor tissue sample available from the metastatic setting (preferably) for retrospective HER2 central analysis confirmed by central laboratory. An adequate sample of tumor tissue must be provided from either a newly acquired biopsy from a region that has not been previously irradiated or the most recent archival sample.
• Patients with Brain Metastases (BM): Eligible if either previously untreated or previously treated BM, provided there is no clinical indication for immediate local therapy. For untreated BM, lesions must be ≤2.0 cm in largest diameter; lesions \>2.0 cm require discussion with and approval from the Medical Monitor. Patients must not require \>3 mg/day of dexamethasone (or equivalent corticosteroid) for symptom control. If receiving anticonvulsants, the regimen must be stable for ≥14 days prior to first dose. A washout period prior enrollment of ≥3 weeks since stereotactic radiosurgery or gamma knife, whole-brain radiotherapy, or radiotherapy or surgery for spinal cord compression is required.
• Note: Patients with leptomeningeal disease may be eligible after discussion with the Medical Monitor.
• Adequate hematologic and end-organ function, defined by the following laboratory results (see protocol)
• LVEF ≥ 50% within 28 days before Cycle 1 Day 1.

You may not qualify if:

• Patients with HER2-negative disease.
• Subjects who, in the opinion of the investigator, are unable to comply with the protocol requirements or who have any comorbidity or condition that may hinder study follow-up, response evaluation, or the informed consent process, including inability to read and understand the local language of the study site sufficiently to interact effectively with study materials and tools (including digital applications).
• Note: Other languages for app-based questionnaires may be provided upon patient request and based on availability of such questionnaires and tools.
• History of other primary malignancy unless treated with curative intent with no evidence of active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence. Exceptions include: basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, in situ cancer of the cervix, curatively treated ductal carcinoma in situ (DCIS), contralateral breast cancer, Stage 1, grade 1 endometrial carcinoma or other solid malignant tumors with an expected curative outcome after Medical Monitor approval.
• Persistent toxicities that the investigator deems related to previous anti-cancer therapy (excluding alopecia), not yet resolved to grade ≤ 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included (e.g., hearing loss). Participants with stable Grade 2 toxicities (defined as no worsening to \>Grade 2 for at least 3 months prior to enrollment and managed with standard of care treatment) may be eligible per the discretion of the investigator (e.g., Grade 2 chemotherapy-induced neuropathy).
• Untreated spinal cord compression
• History of significant cardiovascular disease, defined as:
• New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction of \< 50%.
• Participants with a medical history of myocardial infarction within 6 months before enrollment or symptomatic CHF (NYHA Class II to IV). Participants with troponin levels above upper limit of normal (ULN) at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out myocardial infarction.
• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation (Mean resting corrected QTcF interval \>470ms (females) or \>450msec (males)). Note: Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the Medical Monitor.
• History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Patients with a history of grade 1 drug-induced ILD/pneumonitis, who are now fully recovered, must be discussed with the Medical Monitor for approval.
• Meets one of the following lung criteria:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of study enrollment, prior pneumonectomy (complete), severe asthma, severe chronic obstructive pulmonary disorder (COPD), restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc,).
• Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the electronic Case Report Form (eCRF) for participants who are included in the study.
• Received a live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study treatment.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Westdeutsche Studiengruppe GmbH (WSG): collaborator
• UNICANCER: collaborator

Study Sites (27)

Gustave Roussy

Villejuif, 94805, France

NOT YET RECRUITING

Klinikum der Universitaet Muenchen AöR

München, Germany

NOT YET RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, Barcelona, 08035, Spain

RECRUITING

Complexo Hospitalario Universitario A Coruna

A Coruña, Spain

NOT YET RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, Spain

RECRUITING

Hospital Universitario de Badajoz

Badajoz, Spain

RECRUITING

Hospital Clínic de Barcelona

Barcelona, Spain

RECRUITING

Hospital Universitario de Basurto

Bilbao, Spain

NOT YET RECRUITING

Institut Català d'Oncologia (ICO) Girona

Girona, Spain

NOT YET RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, Spain

RECRUITING

Institut Català d'Oncologia (ICO) Hospitalet

L'Hospitalet de Llobregat, Spain

NOT YET RECRUITING

Hospital Universitario Leon

León, Spain

RECRUITING

Hospital Universitari Arnau De Vilanova De Lleida

Lleida, Spain

NOT YET RECRUITING

Hospital 12 Octubre

Madrid, Spain

RECRUITING

Hospital Universitario De Fuenlabrada

Madrid, Spain

NOT YET RECRUITING

Hospital Universitaro Ramón y Cajal

Madrid, Spain

NOT YET RECRUITING

Hospital Regional Universitario de Málaga

Málaga, Spain

RECRUITING

Hospital Son Espases

Palma de Mallorca, Spain

RECRUITING

Hospital Sant Joan de Reus

Reus, Spain

RECRUITING

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

NOT YET RECRUITING

Hospital Universitario de Valdecilla

Santander, Spain

NOT YET RECRUITING

Centro Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, Spain

NOT YET RECRUITING

Hospital Universitario Virgen Del Rocío

Seville, Spain

NOT YET RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, Spain

NOT YET RECRUITING

Instituto Valenciano de Oncologia (IVO)

Valencia, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Valladolid

Valladolid, Spain

RECRUITING

Hospital Universitario Lozano Blesa

Zaragoza, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Mariana Paes Dias, PhD

CONTACT

+34 933 436 302; info@gruposolti.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2025
• First Posted: January 28, 2026
• Study Start: February 18, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): July 1, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

DE (1); FR (1); ES (25)