None listed
Conditions
Interventions
Drug : Experimental : Durvalumab 1120mg IV D1 plus Dato-DXd 6.0mg/kg IV D1
Active Comparator: Dato-DXd 6.0mg/kg IV D1
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1.Willing and able to provide written informed consent 2.Ability to comply with the protocol 3.Female = 18 years of age 4.Triple-negative disease, defined as tumour cells being: •Negative for ER with 2500/µL (2.5 x 109/L) •Platelet count = 100,000/µL (100 x 109/L) (transfusion not permitted within 28 days of study medication) •Haemoglobin = 9.0 g/dL (90g/L) with no blood transfusions (packed red blood cells) •Serum albumin = 3g/dL •AST (SGOT) or ALT (SGPT) and ALP = 2.5 times the institutional upper limit of normal (ULN), bilirubin = 1.5 x ULN (patients with liver metastases who have AST or ALT = 5 x the institutional ULN may be enrolled) •aPTT = 1.5 × the institutional ULN, INR <1.5 and absence of evidence of impaired hepatic synthesis function. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose •Serum Creatinine = 1.5 x institutional ULN •Glomerular filtration rate = 40mL/min as assessed by standard methodology at the investigating center (i.e., Cockcroft Gault, MDRD or CKD-EPI formulae, EDTA clearance or 24 h urine collection) •No evidence of haematuria: +++ on microscopy or dipstick 11.Patients of childbearing potential are eligible provided they have a negative serum or urine pregnancy test on Cycle 1, Day 1 (within 72 hours) of study treatment, preferably as close to the first dose as possible. Patients must agree to use adequate contraception, defined as those methods with a failure rate of < 1 % per year beginning 14 days before the first dose of study drug and for 7 months after the last dose of study drug. Also, participants must not donate, or retrieve for their own use, ova at any time during this study and for at least 7 months after the last dose of treatment. Preservation of ova should be considered prior to randomisation or the first d
Exclusion criteria
Exclusion criteria: 1.Prior chemotherapy, immunotherapy (including durvalumab) or treatment with PARP inhibitors for advanced or metastatic breast cancer 2.Prior treatment with immune checkpoint inhibitors (eg atezolizumab, pembrolizumab) or DNA topoisomerase I or TROP2- or HER2-targeting ADCs and TROP2 targeted therapy in the (neo)adjuvant setting within 6 months from the end of treatment and randomisation into this study 3.Patients with prior allogeneic stem cell or solid organ transplantation. 4.Patients must not have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent), or had oral or IV steroids for 14 days prior to the first dose of study drug; the use of intranasal, inhaled corticosteroids topical steroids, or local steroid injections, physiologic replacement doses of glucocorticoids (i.e. for adrenal insufficiency) and mineralocorticoids (e.g. fludrocortisone) or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication is allowed. 5.Administration of a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 6.Active or prior documented autoimmune or inflammatory disorders including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, , rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis , Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The following are exceptions to this criterion: •Patients with vitiligo or alopecia •Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy •Any chronic skin condition that does not require systemic therapy •Patients without active disease in the last 5 years may be included •Patients with celiac disease controlled by diet alone 7.History of idiopathic pulmonary fibrosis (including pneumonitis or interstitial lung disease), drug-induced pneumonitis, radiation pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) requiring steroids, or evidence of active pneumonitis on screening chest CT scan. 8.Active infection requiring systemic therapy. 9.History of HIV infection 10.Known active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 11.Known history of active tuberculosis (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). 12.Any other disease, metabolic dysfunction, physical examination finding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) ;Objective Response Rate (ORR) : as the proportion of the patients in the analysis population who have a complete response (CR) or partial response (PR);Duration of Response(DoR) : as the time from first documentation of CR or PR to confirmed disease progression;Clinical Benefit Rate (CBR) ;Duration of Clinical Benefit(DoCB);Patient reported outcome (PROs);Incidence, nature and severity of adverse events with severity determined according to CTCAE v5.0. | — |
Countries
Korea, Republic of
Contacts
Public ContactHyangki Lee
Asan Medical Center
Outcome results
None listed