Informations générales (source: ClinicalTrials.gov)
Patient-Centered Study of Trastuzumab Deruxtecan (T-DXd) in First-Line HER2-Positive Metastatic Breast Cancer With Proactive Toxicity Management Reflecting Real-World Clinical Practice
Interventional
Phase 2
SOLTI Breast Cancer Research Group (Voir sur ClinicalTrials)
février 2026
juillet 2030
23 octobre 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Jean ZEGHONDY | 23/10/2026 13:20:02 | Contacter | ||
Critères
Tous
1. 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.
2. Male/female patients who are at least 18 years of age on the day of signing informed
consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. 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:
1. 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.
2. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Adequate hematologic and end-organ function, defined by the following laboratory
results (see protocol)
10. LVEF ≥ 50% within 28 days before Cycle 1 Day 1.
11. Life expectancy of ≥ 12 weeks at screening.
12. Adequate treatment washout period before first dose of study intervention, defined
as (see protocol)
13. Male patients and female patients of childbearing potential who engage in
heterosexual intercourse must agree to use protocol-specified highly effective
method of contraception.
14. 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:
- Resilience PRO: Android 8.0 (or newer) OR iOS 15.0 (or newer)
- Cankado PRO-React: Android 13.0 (or newer) OR iOS 17.0 (or newer)
15. Only applicable in France: patients affiliated to the social security system.
Exclusion Criteria:
1. Patients with HER2-negative disease.
2. 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.
3. 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.
4. 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).
5. Untreated spinal cord compression
6. 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.
7. 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.
8. 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.
9. 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.
10. Active serious infection requiring IV antibiotics, antivirals, or antifungals.
11. Active HIV, HBV (defined as having a positive HbsAg test) or HCV.
1. 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.
2. 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.
3. Patients who are HCV antibody positive with polymerase chain reaction negative
for HCV RNA may be eligible
12. 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.
13. Received prior chemotherapy or HER2-targeted therapy for advanced or mBC.
14. 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
15. Requirement for ongoing therapy with or prior use of any prohibited medications.
16. 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.
17. Known hypersensitivity or allergy to T-DXd, their metabolites, formulation
excipient, or other monoclonal antibodies.
18. Positive serum pregnancy test or women who are lactating.
19. Only applicable in France: patients deprived of their liberty or under protective
custody or guardianship.