Authorised Therapeutic exploratory (Phase II) Metastatic Breast Cancer HR+, HER2-

Detection of tumour DNA in the blood of patients receiving standard therapy for hormone receptor-positive (HR+) HER2 low expression (HER2 low or HER2 ultra low) metastatic breast cancer as a tool to select those who may benefit from treatment with the antibody–drug conjugate trastuzumab-deruxtecan, and determine its efficacy.

EU CTIS ID: 2024-515349-41-00

What this study is testing

To assess whether early switch of standard treatment (at 8 weeks), from an endocrine therapy (AI or fulvestrant) plus CDK4/6 inh to trastuzumab deruxtecan (T-DXd) for a population expected to develop resistance to SOC treatment according to the Molecular Response is associated with an improved progression-free survival (PFS).

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

Screening Phase_1. Patient must have signed the written informed consent for screening phase prior to any trial specific procedures
Treatment Phase_5. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to enrolment.
Treatment Phase_6. Participant has adequate bone marrow and organ function within 14 days before enrolment, defined as the following laboratory values: • Absolute neutrophil count (ANC) ≥ 1500/mm3, • platelet count ≥ 100,000/mm3, • haemoglobin ≥ 9.0 g/dl, • Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 30 mL/min, • Serum albumin ≥ 2.5 g/dL, • Total bilirubin ≤1.5 × ULN (<3 ULN if Gilbert’s disease), • In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN. If the participant has liver metastases, ALT and AST < 5 × ULN, he/she will be eligible for the study, • Adequate blood clotting function: defined as an international normalized ratio/prothrombin time ≤ 1.5 × ULN and either partial thromboplastin time or activated partial thromboplastin time within normal limits. Note: Transfusion (red blood cell or platelet) or G-CSF administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to C1D1.
Screening Phase_2. Patient is ≥18 years of age.
Treatment Phase_7. Women of childbearing potential must have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) result within 3 days of enrolment.
Treatment Phase_8. Men or women of childbearing potential must agree to the use of effective contraceptive for the study duration and for at least 7 months after the last dose of study treatment for women, and at least 4 months for men.

You likely can't join if

Screening Phase_1. Patient is eligible to chemotherapy because of visceral crisis (severe organ dysfunction, as assessed by signs and symptoms, laboratory studies and rapid progression of disease). Note : Visceral crisis is not the mere presence of visceral metastases but implies important organ compromise leading to a clinical indication for the most rapidly efficacious therapy.
Treatment Phase_16. Participation in a therapeutic clinical study within 4 weeks before enrolment.
Screening Phase_10. Social, familial, or geographic factors that would interfere with study participation or follow-up.
Treatment Phase_17. Patient is currently pregnant, breastfeeding, or planning to become pregnant
Treatment Phase_18. Patient has substance abuse history or any other medical conditions such as clinically significant cardiac or 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.
Treatment Phase_19. Person deprived of their liberty or under protective custody or guardianship.

See the full eligibility criteria

Who can join

Screening Phase_1. Patient must have signed the written informed consent for screening phase prior to any trial specific procedures
Treatment Phase_5. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to enrolment.
Treatment Phase_6. Participant has adequate bone marrow and organ function within 14 days before enrolment, defined as the following laboratory values: • Absolute neutrophil count (ANC) ≥ 1500/mm3, • platelet count ≥ 100,000/mm3, • haemoglobin ≥ 9.0 g/dl, • Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 30 mL/min, • Serum albumin ≥ 2.5 g/dL, • Total bilirubin ≤1.5 × ULN (<3 ULN if Gilbert’s disease), • In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN. If the participant has liver metastases, ALT and AST < 5 × ULN, he/she will be eligible for the study, • Adequate blood clotting function: defined as an international normalized ratio/prothrombin time ≤ 1.5 × ULN and either partial thromboplastin time or activated partial thromboplastin time within normal limits. Note: Transfusion (red blood cell or platelet) or G-CSF administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to C1D1.
Screening Phase_2. Patient is ≥18 years of age.
Treatment Phase_7. Women of childbearing potential must have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) result within 3 days of enrolment.
Treatment Phase_8. Men or women of childbearing potential must agree to the use of effective contraceptive for the study duration and for at least 7 months after the last dose of study treatment for women, and at least 4 months for men.
Treatment Phase_9. Patient must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
Screening Phase_3. Documented breast cancer that: • Is metastatic and eligible to biopsy for subsequent histological or cytological confirmation • Is HER2 low (HER2 1+, or 2+ and ISH negative) or HER2 ultra low (IHC 0 with incomplete and faint membrane staining in >0 and ≤ 10% of tumour cells) on the most recent tumour material available, as defined by the local pathologist under ASCO/CAP guidelines. • Is HR-positive (positive for estrogen receptor or progesterone receptor ≥ 10% of tumour cell nuclei are immunoreactive) in the metastatic setting.
Screening Phase_4. Patient has either: • a metastatic relapse during or within 1 year after termination of the adjuvant endocrine therapy (AI resistant), or • a metastatic relapse located on either lung and/or liver, and/or other visceral location, occurring more than one year of completing adjuvant AI or a de-novo MBC (AI sensitive/naive).
Screening Phase_6. Patient did not receive any therapy in the metastatic setting.
Screening Phase_7. Patient is eligible for a first-line treatment with a marketed CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) in combination with either AI or fulvestrant, according to its marketing authorisation
Screening Phase_10. Patient has a measurable or an evaluable disease according to RECIST v1.1.
Screening Phase_8. Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
Screening Phase_9. Patient has an adequate bone marrow and organ function.
Screening Phase_11. Availability of an archived metastatic tumour sample (FFPE) for exploratory research. Bone metastasis are accepted if tissue is representative of tumour tissue (at least 10% tumour cellularity).
Screening Phase_12. Patient must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
Screening Phase_13. Registration in a National Health Care System (or equivalent).
Treatment Phase_1. Patient must have signed the written informed consent for the treatment phase prior to any trial specific procedures.
Treatment Phase_2. Patient must have discontinued CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) at least 7 days before enrolment, but no longer than 14 days
Treatment Phase_3. Patients must present a no drop of ctDNA determined by a ctDNA assay after 4 weeks of standard of care treatment with a CDK4/6 inhibitor. A no-drop is defined by a Molecular Response (MR) ≥0.5 according to by MR calculation [Zhang 2020].
Treatment Phase_4. Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.

What rules you out

Screening Phase_1. Patient is eligible to chemotherapy because of visceral crisis (severe organ dysfunction, as assessed by signs and symptoms, laboratory studies and rapid progression of disease). Note : Visceral crisis is not the mere presence of visceral metastases but implies important organ compromise leading to a clinical indication for the most rapidly efficacious therapy.
Treatment Phase_16. Participation in a therapeutic clinical study within 4 weeks before enrolment.
Screening Phase_10. Social, familial, or geographic factors that would interfere with study participation or follow-up.
Treatment Phase_17. Patient is currently pregnant, breastfeeding, or planning to become pregnant
Treatment Phase_18. Patient has substance abuse history or any other medical conditions such as clinically significant cardiac or 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.
Treatment Phase_19. Person deprived of their liberty or under protective custody or guardianship.
Screening Phase_3. Prior exposure to ADC or CDK4/6 inhibitors (in metastatic setting). CDK4/6 inhibitors given in adjuvant setting must be stopped for at least 12 months prior screening
Treatment Phase_20. Social, familial, or geographic factors that would interfere with study participation or follow-up.
Screening Phase_4. Patient who has initiated the CDK4/6 inhibitor treatment.
Screening Phase_5. Patient is unable to swallow tablets.
Screening Phase_6. Patient has a history of (non-infectious) ILD/pneumonitis requiring steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at baseline
Treatment Phase_8. Uncontrolled or significant cardiovascular disease, including any of the following: • History of myocardial infarction within 6 months before enrolment, • History of symptomatic congestive heart failure (New York Heart Association Class II to IV), • Patient with a corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (males) based on average of the screening triplicate12-lead ECG. • Patients with known troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out MI
Screening Phase_7. Patient has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
Screening Phase_8. Patient has a history of severe hypersensitivity reactions to other monoclonal antibodies.
Treatment Phase_1. AI resistant patients who are eligible to SAFIR 03 - ARRIBA trial (i.e. PIK3CA mutated patients), until SAFIR 03 - ARRIBA study closure or study steering committee’s decision.
Screening Phase_9. Person deprived of their liberty or under protective custody or guardianship.
Treatment Phase_21.Patient is eligible to chemotherapy because of visceral crisis (severe organ dysfunction, as assessed by signs and symptoms, laboratory studies and rapid progression of disease). Note : Visceral crisis is not the mere presence of visceral metastases but implies important organ compromise leading to a clinical indication for the most rapidly efficacious therapy
Treatment Phase_2. Patient has received more than 2 cycles of the ongoing CDK4/6 inhibitor treatment combined with either AI or fulvestrant.
Treatment Phase_3. Patient has interrupted the ongoing CDK4/6 inhibitor treatment for more than 14 days.
Treatment Phase_4. Patient has evidence of clinical or radiological disease progression.
Treatment Phase_5. Patient has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.
Treatment Phase_6. Patient has malignancies within 3 years, other than that under study, with the exception of: adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumours curatively treated, or contralateral breast cancer.
Treatment Phase_9. Clinically severe pulmonary compromise resulting from current pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrolment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (i.e., rheumatoid arthritis, Sjögren’s, sarcoidosis, etc.), or prior pneumonectomy.
Treatment Phase_7. Patient is at high medical risk because of severe or uncontrolled systemic disease, such as uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, chronic pancreatitis, chronic active infection with hepatitis B virus, hepatitis C virus, or HIV, active untreated or uncontrolled fungal, bacterial or viral infections, active primary immunodeficiency etc.
Screening Phase_2. Patient has a breast cancer amenable for resection or radiation therapy with curative intent.
Treatment Phase_10. Patient has spinal cord compression or clinically active central nervous system metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
Treatment Phase_11. Major surgery within 4 weeks before study enrolment.
Treatment Phase_12. Patient who has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to enrolment, or who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom ≥ 25% of the bone marrow was irradiated
Treatment Phase_14. Patient receiving drug that may cause QTc prolongations or cardiac arrhythmia. Pimozide (Orap®) and cisapride (Prepulsid®) are strictly contraindicated: they are associated with a major risk of ventricular rhythm disorder.
Treatment Phase_15. Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP.

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.