Locally Advanced Breast CancerPhase 2TRANSCENDERNCT05744375
Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab
A Phase 2 study testing Trastuzumab deruxtecan in people with Locally Advanced Breast Cancer and Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 19 sites in Spain.
Trial summary
The goal of this national, multicenter single arm phase II clinical trial is to study the efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in HER2-positive locally advanced or metastatic breast cancer (MBC) patients resistant to trastuzumab plus pertuzumab plus taxane due to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- Trastuzumab deruxtecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 19 sitesSpain
- Study dates
- 28 Sep 2023to 17 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written and signed informed consent obtained prior to any study-specific procedure.
- Male or female patients of at least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Life expectancy ≥ 12 weeks.
- Recurrent breast cancer that is unresectable locally advanced or metastatic.
- Pathologically documented HER2-positive status by local laboratory determination, preferably on the most recent available Formalin-fixed paraffin-embedded (FFPE) tumor sample, according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay. In case of discordance in HER2 status in different biopsies, the result from the most recent biopsy will be used.
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- Pathologically documented Hormone Receptor (HR)-positive or -negative by local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status in different biopsies, the result from the most recent biopsy will be used.
- Prior anti-HER2 based therapy (with trastuzumab plus pertuzumab plus taxane with or without trastuzumab-emtansine) in the (neo)adjuvant setting with a relapse while on therapy or within 12 months from the end of last anti-HER2 therapy.
- Measurable disease assessed by the investigator based on RECIST version 1.1.
- Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
- Adequate organ and marrow function defined as follows:
- Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 (1.5x109/L).
- Platelet count ≥ 100,000/mm3 (100x109/L).
- Hemoglobin ≥ 9g/dL (90g/L).
- Creatinine clearance ≥ 30 mL/min as calculated using the standard method for the institution.
- Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3.0 x ULN (< 5.0 × ULN in participants with liver metastases).
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases are present).
- Serum albumin ≥ 2.5 g/dL
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
- Negative serum pregnancy test with a sensitivity of at least 25 milliInternational Units per milliliter of urine (mIU/mL) (unless permanent previous sterilization procedure such as bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) for premenopausal women, and for women who have experienced menopause onset < 12 months prior to first dose of therapy.
Who cannot join
- Prior chemotherapy or HER2-targeted therapy for locally advanced or MBC (one prior endocrine therapy regimen for MBC without concurrent anti-HER2 therapy or radiotherapy is allowed).
- Ineligible for treatment with T-DXd.
- Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with patient's participation or study results.
- Patients with spinal cord compression, leptomeningeal disease or clinically active central nervous system (CNS) metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic, and no needing corticosteroids or anticonvulsants may be enrolled in the study.
- Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Lung criteria:
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- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe Chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.).
- Any autoimmune, connective tissue or inflammatory disorders (e.g. 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 patients who are enrolled in the study.
- Prior pneumonectomy.
- Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF), troponin levels consistent with myocardial infarction as defined according to American College of Cardiologists (ACC) guidelines, unstable angina, or serious cardiac arrhythmia requiring treatment. QT interval corrected using Fridericia's formula (QTcF) > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG.
- History of active primary immunodeficiency, known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
- Patients who received before treatment starts:
- Any investigational agent within 4 weeks.
- Chemotherapy within a period of time that is shorter than the cycle duration used for that treatment (e.g. < 3 weeks for fluorouracil, doxorubicine, epirubicin or < 1 week for weekly chemotherapy).
- Targeted therapy (e.g., antibodies): up to 4 weeks prior to starting study treatment.
- Endocrine therapy: tamoxifen or aromatase inhibitor within 2 weeks prior to starting study treatment.
- Radiotherapy within 2 weeks prior to starting study treatment. Patients who received prior radiotherapy to >25% of bone marrow are not eligible regardless of when it was administered.
- Major surgery or other anti-cancer therapy not previously specified within 4 weeks prior to starting study treatment.
- In any case, resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI-CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion) is mandatory.Patients may be enrolled with chronic, 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) that the investigator deems related to previous anticancer therapy, such as: chemotherapy-induced neuropathy or fatigue and immunotherapy-induced toxicities (e.g. endocrinopathies as hypothyroidism/hyperthyroidism, type 1 diabetes, hypoglycemia, adrenal insufficiency, adrenalitis and skin hypopigmentation [vitiligo]).
- Have a diagnosis of any other malignancy within 3 years prior to inclusion, except for adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated and contralateral breast cancer.
- Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd.
- Prior treatment with T-DXd or allergic reaction to trastuzumab.
- Patient is pregnant or breastfeeding or planning to become pregnant within the projected duration of the trial, starting at screening and through 7 months after the last dose of the study treatment. Male patients whose partners plan to become pregnant within the duration of the trial, starting at screening and through 4 months after the last dose of the study treatment.
- ✓ For premenopausal women it is necessary an agreement to remain complete abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study treatment.
- Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal litigation, male sterilization, and certain intrauterine devices (provided coils are copper banded).
- Alternative, two methods (e.g. two barrier methods such as a condom and a cervical cap or combined with estrogen and progestogen) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
- Female patients must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.
- ✓ For men it is necessary an agreement to remain complete abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and to refrain from donating sperm during the same period, as defined below with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of study treatment to avoid exposing the embryo.
- Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- Uncontrolled intercurrent illness including uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
- Has substance abuse or any other medical/psychological conditions that may, in the opinion of the investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Spain19 sites
Complejo Hospitalario Universitario A Coruña (CHUAC)
A Coruña, 15006
Hospital San Juan de Alicante
Alicante, 03550
Hospital Universitario de Badajoz
Badajoz, 06080
Hospital del Mar
Barcelona, 08003
Hospital Universitario San Pedro de Alcántara
Cáceres, 10003
Hospital Universitario de Jeréz De La Frontera
Cadiz, Andalusia, 11407
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28942
Hospital Galdakao-Usansolo
Galdakao, Vizcaya, 48960
Hospital Universitario Clínico San Cecilio
Granada, 18016
Hospital Universitario de Jaén
Jaén, Andalusia, 23007
Hospital Universitario Arnau de Vilanova de Lleida
Lleida, 25198
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda, Madrid, 28222
Hospital Universitario Son Espases
Palma de Mallorca, Mallorca, 07120
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, 39008
Hospital Universitario Virgen del Rocío
Seville, 41013
About this study
Official title: Phase II Trial of TRAstuzumab deruxtecaN in firSt-line Treatment of HER2-positive Locally advanCEd or Metastatic Breast caNcer (MBC) Patients Considered Resistant to Trastuzumab + Pertuzumab + Taxane Due to Early Relapse."TRANSCENDER Study"
The goal of this national, multicenter single arm phase II clinical trial is to study the efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in HER2-positive locally advanced or metastatic breast cancer (MBC) patients resistant to trastuzumab plus pertuzumab plus taxane due to early relapse.
The main questions it aims to answer are:
- To evaluate the antitumor activity of T-DXd in the first-line treatment of HER2-positive breast cancer patients resistant to trastuzumab-pertuzumab based therapy.
- To assess other efficacy measures.
- To evaluate safety and tolerability in all patients enrolled in the study.
- To evaluate health-related quality of life (HRQoL). Forty-one evaluable patients will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). Patients will receive T-DXd until unacceptable toxicity, progressive disease, informed consent withdrawal, or other discontinuation criterion is met.
Read the detailed description
This is a national, multicenter single arm phase II clinical trial to study the efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in HER2-positive locally advanced or MBC patients resistant to trastuzumab plus pertuzumab plus taxane due to early relapse.
Eligible patients will be enrolled and treated with T-DXd 5.4 mg/kg IV every 3 weeks.
The T-DXd dose will be recalculated in the event that patients experience body weight variations greater than 10% during the treatment period.
All patients enrolled will receive study therapy until radiographic or symptomatic progressive disease, unacceptable toxicity or withdraw of the informed consent, whatever occurs first.
Study population:
HER2-positive locally advanced or MBC patients who have not received prior chemotherapy or HER2 targeted therapy for advanced disease and with a Disease-Free Interval (DFI) of <12 months from the end of prior (neo)adjuvant anti-HER2 therapy.
Study Duration: The start date of the study is the date of the first site activation. Recruitment period will occur during approximately 24 months from the first patient in.
The end date of the study is the date of the last visit of the last patient (LPLV), including follow-up. The duration of the study will be approximately 68 months from the first patient in.
Performing exploratory objectives will be independent of the date of the end of the study.
- Being tested
- Trastuzumab deruxtecan
- Keywords
- Trastuzumab deruxtecan, HER2-positive, Advanced Breast Cancer, Metastatic Breast Cancer, resistant to prior (neo) adjuvant anti-HER2 therapy.
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecanDrug
Also called Enhertu
All patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days).
The subject's weight at baseline will be used to calculate the initial dose. If during the course of treatment the subject's weight changes by ± 10% of the baseline weight, the subject's dose will be recalculated based on the subject's updated weight.
Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD), informed consent withdrawal, or other discontinuation criterion is met.
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | Experimental | All patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days).
The subject's weight at baseline will be used to calculate the initial dose. If during the course of treatment the subject's weight changes by ± 10% of the baseline weight, the subject's dose will be recalculated based on the subject's updated weight.
Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD), informed consent withdrawal, or other discontinuation criterion is met. Receives: Drug: Trastuzumab deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the rate of complete response (CR) plus partial response (PR) based on the investigator's assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment (efficacy population).
Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions.
The ORR will be reported, including a 95% Confidence Interval (CI) using the Clopper-Pearson method.
A sensitivity analysis will be performed using the Intent to treat population (ITT) population.
Measured: Through study treatment, and average of 18 months
Secondary outcomes (7)
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from the date of enrollment to the date of disease progression, based on the investigator's assessment using RECIST version 1.1., or death from any cause, whichever occurs first.
PFS data will be censored on the date of the last tumor assessment on study for patients who do not have objective tumor progression and who have not died due to any cause while on study. Additionally, patients who start a new anti-cancer therapy prior to documented progression disease (PD) will be censored at the date of the last tumor assessment prior to the start of the new therapy. PD is defined using RECIST, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
PFS analysis will be performed in the safety population. PFS will be assessed using the Kaplan-Meier method. The median event time and 95% CI will be estimated if reached.
Measured: Through study treatment, and average of 18 months
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of enrollment to the date of death from any cause.
OS data will be censored on the last date the patient is known to be alive. OS analysis will be performed in the safety population. OS will be assessed using the Kaplan-Meier method. The median event time and 95% CI will be estimated if reached.
Measured: Through study, and average of 36 months
Time to Treatment Response (TTR)
Time to treatment response (TTR) is defined as the time from the date of enrollment to the date of first documentation of objective tumor response (CR or PR).
TTR analysis will be performed in the efficacy population in patients with an Objective Response (OR).
TTR will be assessed using the Kaplan-Meier method. The median event time and 95% CI will be estimated.
Measured: Through study treatment, and average of 18 months
Duration of Response (DoR)
Duration of response (DoR) is defined as the time from the date of first documentation of objective tumor response (CR or PR) to the date of first documented progressive disease based on the investigator's assessment using RECIST version 1.1., or death from any cause, whichever occurs first.
DoR will be censored on the date of the last tumor assessment on study for patients who do not have objective tumor progression and who have not died due to any cause while on study. Additionally, patients who start a new anti-cancer therapy prior to documented PD will be censored at the date of the last tumor assessment prior to the start of the new therapy.
DoR analysis will be performed in the efficacy population in patients with an OR.
DoR will be estimated using Kaplan-Meier methods. The median event time and 95% CI will be estimated if reached.
Measured: Through study treatment, and average of 18 months
The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment
Safety assessments will be performed at baseline and during the study: Vital signs assessments (blood pressure, pulse and body temperature), measurement of left ventricular ejection fraction, triplicate 12-lead electrocardiogram, laboratory assessments (hemoglobin, White Blood Cell, Absolute Neutrophil Count, Lymphocytes, platelet count, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, serum creatinine, creatinine clearance, sodium, potassium, total calcium, blood urea nitrogen (or urea), albumin, Troponin Test, Coagulation testing (International Normalized Ratio, activated partial thromboplastin time), pregnancy test , ophthalmologic assessments (visual acuity testing, slit lamp examination, fundoscopy), Viral serology.
AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
The toxicity of study treatments will be evaluated in the safety population.
Measured: Through study treatment, and average of 18 months
Changes From Baseline in the Global Health Status Score (GHS)
Change from baseline in the GHS and each scale of the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) will be presented at each scheduled time point for the GHS score and each of the functionals and symptoms scales from the QLQ-C30 questionnaires. Longitudinal analysis of scores will be performed using linear mixed models.
QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items.
Each of the multi-item scales includes a different set of items - no item occurs in more than one scale.
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Thus a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: Through study treatment, and average of 18 months
Time to Deterioration (TTD) in Quality of Life (QoL)
Time to deterioration (TTD) in QoL is defined as the time from the date of enrollment to the date of first detection of a deterioration event. A deterioration event is defined as an increase of ≥ minimally important difference (MID) from baseline for the EORTC QLQ-C30 symptom scales and a decrease of ≥ MID from baseline for the EORTC QLQ-C30 functional scales and GHS scale. It will be assessed using the Kaplan-Meier. Method. The median event time and 95% CI for the median will be estimated if reached. TTD will be censored at the date of the last QoL assessment prior to the start of a new therapy.
Measured: Through study treatment, and average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2023
- Study start28 Sep 2023
- Primary completion17 Jul 2025
- Study completion17 Jul 2025
Why it stopped: The study stopped due to insufficient accrual (only two patients were included), and the sponsor has decided on its premature termination.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spanish Breast Cancer Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Study Director Study Director, Study director, Hospital General Universitario Gregorio Marañón. Madrid, Spain.Study Director Study Director, Study director, Hospital del Mar. Barcelona, Spain.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05744375
- Sponsor's protocol ID
- GEICAM/2021-08
- Other IDs
- 2023-503627-26-00, 2023
- Acronym
- TRANSCENDER
- Status last verified
- Mar 2026
- First submitted
- 15 Feb 2023
- Last updated
- 2 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of TRAstuzumab deruxtecaN in firSt-line Treatment of HER2-positive Locally advanCEd or Metastatic Breast caNcer (MBC) Patients Considered Resistant to Trastuzumab + Pertuzumab + Taxane Due to Early Relapse."TRANSCENDER Study"
- ClinicalTrials.gov ID
- NCT05744375
- Acronym / sponsor ID
- TRANSCENDER / GEICAM/2021-08
- Keywords
- Trastuzumab deruxtecan, HER2-positive, Advanced Breast Cancer, Metastatic Breast Cancer, resistant to prior (neo) adjuvant anti-HER2 therapy.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study stopped due to insufficient accrual (only two patients were included), and the sponsor has decided on its premature termination.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Spanish Breast Cancer Research GroupUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 28 Sep 2023 (actual)
- Primary completion
- 17 Jul 2025 (actual)
- Study completion
- 17 Jul 2025 (actual)
- First posted
- 27 Feb 2023 (actual)
- Results
- Posted 12 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this national, multicenter single arm phase II clinical trial is to study the efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in HER2-positive locally advanced or metastatic breast cancer (MBC) patients resistant to trastuzumab plus pertuzumab plus taxane due to early relapse.
The main questions it aims to answer are:
- To evaluate the antitumor activity of T-DXd in the first-line treatment of HER2-positive breast cancer patients resistant to trastuzumab-pertuzumab based therapy.
- To assess other efficacy measures.
- To evaluate safety and tolerability in all patients enrolled in the study.
- To evaluate health-related quality of life (HRQoL). Forty-one evaluable patients will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). Patients will receive T-DXd until unacceptable toxicity, progressive disease, informed consent withdrawal, or other discontinuation criterion is met.
Detailed description
This is a national, multicenter single arm phase II clinical trial to study the efficacy, safety and tolerability of the administration of Trastuzumab Deruxtecan (T-DXd) in HER2-positive locally advanced or MBC patients resistant to trastuzumab plus pertuzumab plus taxane due to early relapse.
Eligible patients will be enrolled and treated with T-DXd 5.4 mg/kg IV every 3 weeks.
The T-DXd dose will be recalculated in the event that patients experience body weight variations greater than 10% during the treatment period.
All patients enrolled will receive study therapy until radiographic or symptomatic progressive disease, unacceptable toxicity or withdraw of the informed consent, whatever occurs first.
Study population:
HER2-positive locally advanced or MBC patients who have not received prior chemotherapy or HER2 targeted therapy for advanced disease and with a Disease-Free Interval (DFI) of <12 months from the end of prior (neo)adjuvant anti-HER2 therapy.
Study Duration: The start date of the study is the date of the first site activation. Recruitment period will occur during approximately 24 months from the first patient in.
The end date of the study is the date of the last visit of the last patient (LPLV), including follow-up. The duration of the study will be approximately 68 months from the first patient in.
Performing exploratory objectives will be independent of the date of the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | Experimental | Drug: Trastuzumab deruxtecanAll patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). The subject's weight at baseline will be used to calculate the initial dose. If during the course of treatment the subject's weight changes by ± 10% of the baseline weight, the subject's dose will be recalculated based on the subject's updated weight. Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD), informed consent withdrawal, or other discontinuation criterion is met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Written and signed informed consent obtained prior to any study-specific procedure.
- Male or female patients of at least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Life expectancy ≥ 12 weeks.
- Recurrent breast cancer that is unresectable locally advanced or metastatic.
Key exclusion criteria (31 listed)
- Prior chemotherapy or HER2-targeted therapy for locally advanced or MBC (one prior endocrine therapy regimen for MBC without concurrent anti-HER2 therapy or radiotherapy is allowed).
- Ineligible for treatment with T-DXd.
- Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with patient's participation or study results.
- Patients with spinal cord compression, leptomeningeal disease or clinically active central nervous system (CNS) metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic, and no needing corticosteroids or anticonvulsants may be enrolled in the study.
- Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab deruxtecanAlso: EnhertuAll patients enrolled will be treated with trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV every 3 weeks (± 3 days). The subject's weight at baseline will be used to calculate the initial dose. If during the course of treatment the subject's weight changes by ± 10% of the baseline weight, the subject's dose will be recalculated based on the subject's updated weight. Patients will receive T-DXd until unacceptable toxicity, progressive disease (PD), informed consent withdrawal, or other discontinuation criterion is met. | Drug | Trastuzumab deruxtecan (T-DXd) |
Primary outcome
Objective Response Rate (ORR)
Time frame: Through study treatment, and average of 18 months
Objective Response Rate (ORR) is defined as the rate of complete response (CR) plus partial response (PR) based on the investigator's assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment (efficacy population). Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions. The ORR will be reported, including a 95% Confidence Interval (CI) using the Clopper-Pearson method. A sensitivity analysis will be performed using the Intent to treat population (ITT) population.
7 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Through study treatment, and average of 18 months
Overall Survival (OS)
Time frame: Through study, and average of 36 months
Time to Treatment Response (TTR)
Time frame: Through study treatment, and average of 18 months
Duration of Response (DoR)
Time frame: Through study treatment, and average of 18 months
The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment
Time frame: Through study treatment, and average of 18 months
Changes From Baseline in the Global Health Status Score (GHS)
Time frame: Through study treatment, and average of 18 months
Time to Deterioration (TTD) in Quality of Life (QoL)
Time frame: Through study treatment, and average of 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research GroupLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director Study Director study director
Hospital General Universitario Gregorio Marañón. Madrid, Spain.
Study Director Study Director study director
Hospital del Mar. Barcelona, Spain.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab deruxtecan in people with Locally Advanced Breast Cancer and Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 19 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Through study treatment, and average of 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.