TRASTUZUMAB DERUXTECAN for HER2-positive locally advanced or metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- 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. Signed informed consent must be obtained prior to any trial-specific screening"}
• {"criterion_text":"- LVEF ≥ 50% within 28 days before Cycle 1 Day 1."}
• {"criterion_text":"- Life expectancy of ≥ 12 weeks at screening."}
• {"criterion_text":"- Adequate treatment washout period before first dose of study intervention, defined as:"}
• {"criterion_text":"- Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified highly effective method of contraception."}
• {"criterion_text":"- Access to a smartphone with internet connection that allows them to carry out the required assessments at the specified timepoints and with the following characteristics: •\tResilience PRO: Android 8.0 (or newer) OR iOS 15.0 (or newer) •\tCankado PRO-React: Android 13.0 (or newer) OR iOS 17.0 (or newer)"}
• {"criterion_text":"- Male/female patients who are at least 18 years of age on the day of signing informed consent."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2."}
• {"criterion_text":"- 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: a)\tHER2-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. b)\tDocumented 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 ≥21 days 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."}
• {"criterion_text":"- Adequate hematologic and end-organ function, defined by the following laboratory results:"}
• {"criterion_text":"- Only applicable in France: patients affiliated to the social security system."}

Exclusion criteria

• {"criterion_text":"- Patients with HER2-negative disease."}
• {"criterion_text":"- Only applicable in France: patient deprived of their liberty or under protective custody or guardianship."}
• {"criterion_text":"- Active HIV, HBV (defined as having a positive HbsAg test) or HCV. a) Participants with a known history of human immunodeficiency virus (HIV) are eligible, if viral load is undetectable for ≥ 6 months prior to enrollment, and subjects are receiving effective anti-retroviral HIV therapy, if indicated. HIV testing is not required for subjects without a known history of HIV, unless mandated by a local health authority. b) For patients with a known history of HBV infection, a hepatitis B core antibody test should be conducted at screening. If positive, hepatitis B DNA testing will be performed and if active HBV infection is ruled out, the patient may be eligible. c) Patients who are HCV antibody positive with polymerase chain reaction negative for HCV RNA may be eligible."}
• {"criterion_text":"- Other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations."}
• {"criterion_text":"- Received prior chemotherapy or HER2-targeted therapy for advanced or mBC."}
• {"criterion_text":"- Prior exposure in the adjuvant setting to an antibody-drug conjugate containing an exatecan derivative (topoisomerase I inhibitor), with a disease-free interval of less than 12 months since the last dose"}
• {"criterion_text":"- Requirement for ongoing therapy with or prior use of any prohibited medications."}
• {"criterion_text":"- Participation in other studies involving investigational drug(s) within 30 days prior to enrollment or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of the Medical Monitor is required to establish eligibility"}
• {"criterion_text":"- Known hypersensitivity or allergy to T-DXd, their metabolites, formulation excipient, or other monoclonal antibodies."}
• {"criterion_text":"- Positive serum pregnancy test or women who are lactating."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Untreated spinal cord compression"}
• {"criterion_text":"- History of significant cardiovascular disease, defined as: •\tNew York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction of < 50%. •\tParticipants 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. •\tHistory 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Meets one of the following lung criteria: •\tLung-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,). •\tAny 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."}
• {"criterion_text":"- 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. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of study treatment."}
• {"criterion_text":"- Active serious infection requiring IV antibiotics, antivirals, or antifungals."}

Primary endpoints

• {"endpoint_text":"- TFST, 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.","definition_or_measurement_approach":"Measured as time (days) from first dose to first subsequent anti-cancer therapy after progression or discontinuation of maintenance treatment, or death (whichever first) as defined in protocol."}
• {"endpoint_text":"- Time to a 10% physical functioning deterioration based on the EORTC QLQ-C30 Physical Functioning scale.","definition_or_measurement_approach":"Measured using the EORTC QLQ-C30 Physical Functioning scale; endpoint is time until a 10% deterioration from baseline on that scale."}

Secondary endpoints

• {"endpoint_text":"- Safety and tolerability will be evaluated in terms of occurrence and severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions, median absolute and relative dose intensity, and median treatment duration.","definition_or_measurement_approach":"Safety assessed by AE occurrence/severity, labs, treatment discontinuations, dose modifications, dose intensity metrics and median treatment duration (as recorded in eCRF)."}
• {"endpoint_text":"- Proportion of participants with maintained or improved treatment-related self-reported symptoms (PRO-CTCAE).","definition_or_measurement_approach":"Measured by PRO-CTCAE instruments; proportion of participants with maintained or improved treatment-related self-reported symptoms."}
• {"endpoint_text":"- Safety and tolerability will be evaluated in terms of occurrence and severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions, median absolute and relative dose intensity, and median treatment duration.","definition_or_measurement_approach":"Same as other safety endpoint (occurrence/severity of AEs, labs, discontinuations, dose changes, dose intensity, median treatment duration)."}
• {"endpoint_text":"- Type and frequency of concomitant medications administered for AE management or supportive care interventions and number of hospitalizations for SAEs","definition_or_measurement_approach":"Captured concomitant medication use for AE management/supportive care and count of hospitalizations for SAEs from medical records and eCRF."}
• {"endpoint_text":"- Percentage of any acute or delayed nausea and vomiting or breakthrough anti-emetic use, in patients receiving prophylactic anti-emetic agents (combination regimen of 3 medicinal products)","definition_or_measurement_approach":"Proportion of patients with acute/delayed nausea/vomiting or breakthrough anti-emetic use among those on specified prophylactic regimen."}
• {"endpoint_text":"- Composite of ER visits, unplanned hospitalizations and non-programed visits","definition_or_measurement_approach":"Composite endpoint combining counts of emergency room visits, unplanned hospitalizations and unscheduled visits."}
• {"endpoint_text":"- PFS, defined as the time from the date of first dose to the date of first clinical or radiological progression or death due to any cause, whichever occurs first, as assessed by the investigators’ assessments and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.","definition_or_measurement_approach":"Measured per investigators' RECIST v1.1 assessments; time from first dose to first clinical/radiological progression or death."}
• {"endpoint_text":"- Overall response rate (ORR), defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) as per local investigator’s assessment and according to RECIST 1.1.","definition_or_measurement_approach":"ORR per local investigator assessment using RECIST 1.1 (CR or PR)."}
• {"endpoint_text":"- Clinical benefit rate (CBR), defined as the proportion of patients with a best overall response of i) CR or PR or ii) SD or Non-CR/Non-PD lasting more than 24 weeks, as per local investigator’s assessment and according to RECIST 1.1.","definition_or_measurement_approach":"CBR per local investigator and RECIST 1.1: CR/PR or SD/Non-CR/Non-PD lasting >24 weeks."}
• {"endpoint_text":"- Time to response (TtR), defined as the time from the date of first dose to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR.","definition_or_measurement_approach":"Time from first dose to first documented objective tumor response (≥30% shrinkage) among responders."}
• {"endpoint_text":"- Duration of response (DoR), defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression, as per local investigator’s assessment and according to RECIST 1.1., or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Time from first documented CR/PR to progression or death as per RECIST 1.1 assessments."}
• {"endpoint_text":"- Proportion of participants experiencing treatment-related symptoms as measured by selected scales from the EORTC QLQ-C30 and EORTC QLQ-BR42.","definition_or_measurement_approach":"Measured via selected scales of EORTC QLQ-C30 and QLQ-BR42 instruments; proportion experiencing treatment-related symptoms."}
• {"endpoint_text":"- Change from baseline in the global health status (GHS)/QoL scale from the EORTC QLQ-C30 questionnaire version 3.0 and functioning scales scores (including physical and role function).","definition_or_measurement_approach":"Change from baseline on EORTC QLQ-C30 GHS/QoL and functioning scales (v3.0)."}
• {"endpoint_text":"- Time to a 10% deterioration in the GHS/QoL scale and other scales from the EORTC QLQ-C30 questionnaire version 3.0.","definition_or_measurement_approach":"Time from baseline to ≥10% deterioration in EORTC QLQ-C30 GHS/QoL and other scales."}
• {"endpoint_text":"- Adherence to digital health tools (ePRO surveys and oximeter measurements)","definition_or_measurement_approach":"Measured by completion rates/adherence metrics for ePRO surveys and oximeter measurements recorded in digital platforms."}
• {"endpoint_text":"- System usability scale, quality of care, quality of communication and overall satisfaction (ad hoc questionnaire encompassing all these domains)","definition_or_measurement_approach":"Assessed via ad hoc questionnaire including System Usability Scale and domains on quality of care/communication and satisfaction."}
• {"endpoint_text":"- Reach and adoption rates, alert rate, and time for Healthcare Professionals (HCPs) to handle alerts, clinical actions taken by HCPs to manage alerts, education content consumption, start and completion of self-management modules (Resilience only); duration of monitoring, number and frequency of visits triggered by the digital systems used over the course of therapy (CANKADO only).","definition_or_measurement_approach":"Digital tool metrics: reach/adoption, alert rates and handling time, clinical actions, education content consumption, self-management module metrics (Resilience) and monitoring/visit triggers (Cankado)."}
• {"endpoint_text":"- Comparative studies of outcome factors (e.g. physical functioning scale, global health status, pain symptom, TTD, digital adherence) in subgroups defined by individual patient characteristics, population, and software solution.","definition_or_measurement_approach":"Comparative subgroup analyses of listed outcome factors by patient characteristics, population and software solution."}

Spain

Earliest CTIS Part Ii Submission Date

16-12-2025

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

43

Number Of Sites

25

Number Of Participants

125

France

Earliest CTIS Part Ii Submission Date

04-11-2025

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

146

Number Of Sites

22

Number Of Participants

100

Germany

Earliest CTIS Part Ii Submission Date

22-12-2025

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

135

Number Of Sites

15

Number Of Participants

75

Primary sponsor

Full Name

Solti Group

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Servicio De Asesoria A La Investigacion Y Logistica S.L.","duties_or_roles":"6,7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Unicancer","duties_or_roles":"15 (Local Partner)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"WSG Westdeutsche Studiengruppe GmbH","duties_or_roles":"15 (Local Partner)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Fundacion Sector Publico Estatal Centro Nacional Investigaciones Oncologicas Carlos III","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"15 (IP labelling and IP distribution)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Asphalion S.L.","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Resilience","duties_or_roles":"15 (Software distribution)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Hospital Universitari Vall D Hebron","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Eurofins Megalab S.A.","duties_or_roles":"15 (Kits and Sample logistics)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"14,3","organisation_type":"Non-Pharmaceutical company"}