None listed
Conditions
Interventions
Drug : "
Experimental Treatment Group : Trastuzumab deruxtecan 5.4mg/kg given intravenously every 3 weeks.
Control Treatment Group : Endocrine therapy of physician's choice[TPC] (Fulvetrant, Fulvestra
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: (1) Histologically or cytologically confirmed hormone receptor-positive advanced breast cancer patients a) Have recurrent, metastatic, or unresectable disease b) Have HER2-low expression status, defined as IHC 2+/ISH- or IHC 1+,with a validated assay by ASCO/CAP guidelines c) Have no previous history of HER2-positive breast cancer (IHC 3+ or ISH+) by ASCO/CAP guidelines d) The hormone receptor (HR) status is defined by ER/PR IHC nuclear staining, and ER or PgR =1% is defined as hormone receptor-positive status (2) Patients who progressed on 1st line endocrine + CDK4/6 inhibitor therapy for advanced breast cancer and received no other systemic therapy for advanced breast cancer. The all FDA-approved CDK4/6 inhibitors (palbociclib, ribociclib, and Abemaciclib) are allowed, and combination with aromatase inhibitors or fulvestrant are both allowed. (3) Patients who have received chemotherapy or adjuvant endocrine therapy in the neo-adjuvant or adjuvant setting are eligible. (4) Female patients with =19 years of age (5) Radiologic or objective evidence of disease progression on or after the last systemic therapy prior to starting study treatment (6) Patients must have at least one measurable lesion by RECIST 1.1 criteria, which was not previously irradiated or showed objective progression after irradiation to that lesion (7) Patients must have an adequate tumor tissue sample available for assessment of HER2 by central laboratory and other exploratory biomarker analyses (8) Patients with ECOG performance status 0 or 1 (9) Both pre- and post-menopausal patients are eligible, and pre-menopausal patients should receive ovarian function suppression treatment (GnRH agonist injection or surgical bilateral oophorectomy) while receiving fulvestrant or aromatase inhibitor treatment in the control arm. Postmenopausal status is defined as one of the following -Bilateral oophorectomy in the past -Age = 60 years old -Age 12 months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) with FSH and estradiol in the postmenopausal range according to local normal ranges. (10) Adequate organ function for treatment Adequate organ and bone marrow function within 14 days before randomization/enrolment as described below:” a) Haemoglobin: = 9.0 g/dL NOTE: Participants requiring ongoing transfusions or growth factor support to maintain haemoglobin =9.0 g/dL are not eligible. (Red blood cell transfusion is not allowed within 1 week prior to C1D1) b) Serum albumin: = 2.5 g/dL c) International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time: = 1.5 × ULN d) Absolute neutrophil count (ANC) =1500 cells/mm3 *granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1 ) e) Platelets =100,000 cells/mm3 *Platelet transfusion is not allowed within 1 week prior to C1D1) f) Estimated creatinine clearance =50 mL/min, or serum creatinine <1.5x institution upper limit of normal (ULN) g) Bilirubin=1.5 x ULN *if no liver metastases or < 3×ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline h) AST (SGOT) =2.5 x ULN (5.0 x ULN if hepatic metastases) i) ALT (SGPT) =2.5 x ULN (5.0 x ULN if hepatic metastases) (11) 12-Lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention (12) QTc inte
Exclusion criteria
Exclusion criteria: (1) Previous history of T-DXd or Dato-Dxd treatment for advanced breast cancer (2) Severe Cardiac disease (e.g., uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past year, Left Ventricular Ejection Fraction (LVEF) > grade 2) (3) Patients with a medical history of myocardial infarction (MI) within 6 months before randomization/enrolment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI. (4) Current active hepatic or biliary disease (except for Gilbert syndrome, asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment) (5) Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals (6) 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 T-DXd. (7) Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to >Grade 2 for at least 3 months prior to [randomization/enrollment/Cycle 1 Day 1] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as: ·Chemotherapy-induced neuropathy ·Fatigue ·Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include: a) Hypothyroidism/hyperthyroidism b) Type 1 diabetes c) Hyperglycaemia d) Adrenal insufficiency e) Adrenalitis f) Skin hypopigmentation (vitiligo) (8) Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months prior to study enrollment, severe asthma, severe chronic obstructive pulmonary disorder [COPD], restrictive lung disease, significant pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (i.e.,rheumatoid arthritis, Sjogren’s syndrome, sarcoidosis etc.), and/or prior pneumonectomy. (9) Has as a history of (non-infectious) ILD/ pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.Presence of spinal cord compression, symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery). Patients with treated brain metastases should be neurologically stable (for 4 weeks post treatment and prior to study enrollment) and without steroid therapy over physiologic dose (> 10mg prednisolone/day) for at least 2 weeks before administration of study drug. (10) Significantly altered mental status prohibiting the understanding of the study, or with psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (11) Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Subjects with past or resolved hepatitis B virus (HBV) infection who are anti-HBc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival(PFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival (OS);Objective response rate (ORR);Progression-free survival(PFS2);Drug safety evaluated by CTCAE 5.0;Quality of Life, assessed by patient-reported outcome(PRO) EORTC-QLQ-C30 and EORTC-QLQ-BR23 questionnaire | — |
Countries
Korea, Republic of
Contacts
Public ContactJoo Hyuk Sohn
Yonsei University Health System, Severance Hospital
Outcome results
None listed