Trastuzumab for Metastatic breast cancer | HER3-mutant metastatic breast cancer | HER2-negative metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Molecular screening step: availability of a formalin-fixed paraffin-embedded (FFPE) block with >10% tumor tissue (it is recommended to provide the most recently collected tumor sample).\n- Having received ≥ 2 previous chemotherapy lines for advanced breast cancer\n- Class IV or V somatic ERBB3 mutation as determined on a tumor sample obtained during the molecular screening step\n- ECOG performance status ≤ 2\n- Evaluable disease, per RECIST v1.1 inclusion criteria\n- Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment\n- Adequate organ function: a.Creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines; b.Total bilirubin ≤1.5 X upper limit of normal (ULN), except for patients with known Gilbert’s disease, who may enroll if the conjugated bilirubin is ≤1.5 X ULN; c.Transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 2.5 X ULN (≤ 5 X ULN if the patient has liver metastases)\n- Women of childbearing potential (WCBP) must have a negative serum pregnancy test < 7 days prior to first dose of treatment. A woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as the absence of menses for 12 months without an alternative cause.\n- WCBP (as defined above) and men with partners of childbearing potential must agree to use a highly effective birth control method during the study and for 3 months after completion of investigational treatment.\n- Patients should be eligible for the treatment step according to the investigator’s opinion.\n- Patients must be covered by a health insurance plan.\n- Molecular screening step: the tumor sample must have been obtained less than 5 years before inclusion\n- Molecular screening step: prior signature of a written informed molecular screening consent.\n- Molecular screening step: patients should be eligible for the treatment step according to the investigator’s opinion.\n- Molecular screening step: patients must be covered by a health insurance plan.\n- Molecular screening step: patients able to provide signed informed consent.\n- Age ≥ 18 years\n- Metastatic or unresectable breast cancer\n- HER2-negative (defined as having an IHC 0+, IHC 1+, or IHC 2+ and ISH non-amplified, per ASCO/CAP guidelines) on last assessable tumor sample\n- Patients able to provide signed informed consent."}

Exclusion criteria

• {"criterion_text":"- Having received any prior treatment targeting HER2. Prior treatment with trastuzumab deruxtecan is allowed, per label, in patients with HER2-low metastatic breast cancer (IHC 1+ or 2+, ISH non-amplified)\n- Leptomeningeal metastases\n- Major surgery (including surgery of brain metastases) < 21 days prior to first dose of treatment\n- Evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment\n- Have known myocardial infarction or unstable angina within 24 weeks prior to first dose of study treatment\n- Have clinically significant cardiopulmonary disease such as: • Ventricular arrhythmia requiring therapy, • Uncontrolled hypertension (defined as persistent systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mm Hg on antihy) due to complications of advanced malignancy, • Hypoxia requiring supplementary oxygen therapy except when oxygen therapy is needed only for obstructive sleep apnea, • Presence of ≥ Grade 2 QTc prolongation on screening ECG, • Conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes: o Congenital or acquired long QT syndrome, o\tFamily history of sudden death, o History of previous drug-induced QT prolongation, o\tCurrent use of medications with known and accepted associated risk of QT prolongation\n- Are known carriers of active Hepatitis B or Hepatitis C or have other known chronic liver disease\n- Are known to be positive for human immunodeficiency virus (HIV)\n- Altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent.\n- Patients who have difficulty undergoing trial procedures for geographic, social or psychological reasons\n- Person deprived of liberty or under guardianship\n- History of allergic reactions to trastuzumab or tucatinib or chemically similar drugs\n- Patients who are pregnant, breastfeeding, or planning a pregnancy from time of informed consent until 7 months after the final dose of study drug\n- Inability to swallow pills or having a significant gastro-intestinal disease or a history of surgery which would preclude the adequate oral absorption of medications\n- Having used a strong CYP2C8 inhibitor within a duration of 5 half-lives prior to the first dose of study treatment, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment (see Appendix B and Appendix C)\n- Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-central nervous system (CNS) radiation, or experimental agent ≤ 3 weeks prior to the first dose of study treatment, except gonadotropin releasing hormone (GnRH) agonists\n- Participation in another interventional clinical trial.\n- Symptomatic and untreated brain metastases or brain metastases requiring urgent treatment, or brain metastases requiring a dose > 2 mg of dexamethasone (or equivalent)\n- Whole brain radiotherapy < 21 days prior to first dose of treatment, stereotactic radiotherapy < 7 days prior to first dose of treatment"}

Primary endpoints

• {"endpoint_text":"- Clinical benefit rate (CBR), defined as the proportion of patients who achieved a complete response (CR), a partial response (PR), or had stable disease (SD) for 24 weeks or more, according to the investigator-assessed RECIST v1.1 criteria.","definition_or_measurement_approach":"Clinical benefit rate (CBR) defined as proportion of patients with CR, PR, or SD ≥24 weeks, assessed by investigator per RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Progression-free survival (PFS), defined as the time from inclusion to progression or death; Objective response rate, defined as the proportion of patients who achieved a CR or PR according to the investigator-assessed RECIST v1.1 criteria; and duration of response, defined as the time between the first observation of a PR or a CR, and progressive disease or death","definition_or_measurement_approach":"PFS measured as time from inclusion to progression or death. Objective response rate = proportion with CR or PR per investigator RECIST v1.1. Duration of response = time from first PR/CR to progression or death."}
• {"endpoint_text":"- Adverse Events (AEs) and Serious Adverse Events (SAEs), per CTCAE v5.0, considered by the investigator as related to trastuzumab or tucatinib.","definition_or_measurement_approach":"AEs/SAEs graded per CTCAE v5.0; attribution to study drugs per investigator assessment."}
• {"endpoint_text":"- QLQ-C30 QoL questionnaire with the QLQ-BR42 module will be filled at inclusion, at cycles 1 and 3 and at the end of the treatment.","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 and QLQ-BR42 at specified time points (inclusion, cycles 1 & 3, end of treatment)."}
• {"endpoint_text":"- Exploratory: relationship between biomarkers (including, but not limited to, DNA, RNA and proteins analyses) in blood, plasma, and/or tumor and either (1) presence of an ERBB3 mutation and (2) treatment efficacy.","definition_or_measurement_approach":"Exploratory biomarker analyses of DNA/RNA/proteins in blood/plasma/tumor to correlate with ERBB3 mutation presence and treatment efficacy; specific assays/metrics not defined in CTIS JSON."}

Other endpoints

• {"endpoint_text":"- Exploratory: relationship between biomarkers (including, but not limited to, DNA, RNA and proteins analyses) in blood, plasma, and/or tumor and either (1) presence of an ERBB3 mutation and (2) treatment efficacy.","definition_or_measurement_approach":"Exploratory biomarker analyses of DNA/RNA/proteins in blood/plasma/tumor to correlate with ERBB3 mutation presence and treatment efficacy; specific assays/metrics not defined in CTIS JSON."}

France

Earliest CTIS Part Ii Submission Date

01-08-2025

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

41

Number Of Sites

9

Number Of Participants

20

Primary sponsor

Full Name

Institut Curie

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Eurofins Clinical Trial Supplies France","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Unicancer","duties_or_roles":"Pharmacovigilance","organisation_type":"Hospital/Clinic/Other health care facility"}