A study of efficacy and safety of LAG525 in combination with spartalizumab, or with spartalizumab and carboplatin, or with carboplatin, in patients with advanced triple-negative breast cancer.
- Conditions
- Triple negative breast cancerMedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004865-28-IT
- Lead Sponsor
- OVARTIS PHARMA AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 88
1. Patient is an adult = 18 years old at the time of informed consent, and has signed informed consent before any trial related activities and according to local guidelines
2. Patient has advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Patient has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by central laboratory for eligibility):
- Absolute neutrophil count = 1.5× 109/L
- Platelets = 100 × 109/L
- Hemoglobin = 9.0 g/dL
- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) = 40 mL/min
- Alanine aminotransferase (ALT) < 3 x ULN, except for patients that have tumor involvement of the liver, who may only be included if ALT =5.0 x ULN who are
excluded if ALT > 5 x ULN
- Aspartate aminotransferase (AST) < 3 x ULN, except for patients that have tumor involvement of the liver, who may only be included if AST =5.0 x ULN who are excluded if AST > 5 x ULN
- Total serum bilirubin < 1.5 ULN; or total bilirubin = 3.0 × ULN with direct bilirubin within normal range of the central laboratory in patients with well documented Gilbert’s Syndrome
5. Patient must have measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other loco-regional therapy will only be considered measurable if disease progression at the treated site after completion of therapy is clearly documented).
6. Patient progressed after adjuvant or 1 prior systemic treatment in the advanced setting.
Patients with de novo metastatic disease are eligible if they received 1 prior line of therapy.
7. Patient must have received prior systemic treatment that included taxane-based chemotherapy for adjuvant or metastatic disease.
8. Patient must have a site of disease amenable to biopsy, and must be willing to undergo a new tumor biopsy at screening and during therapy on this study, the latter if medically feasible. Patients with an available archival tumor tissue do not need to perform a tumor biopsy at screening if patient has not received anti-cancer therapy since the biopsy was taken.
9. Patient has histologically and/or cytologically confirmed diagnosis of advanced TNBC (based on most recently analyzed biopsy from locally recurrent or metastatic site, local lab) meeting the following criteria: HER2 negative in situ hybridization test or an IHC status of 0 or 1+, and ER and PR expression is <1 percent as determined by immunohistochemistry (IHC) Hammond et al 2010.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 59
1. Patient has received prior immune checkpoint inhibitors as anticancer treatment, such as anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy).
2. Patient received prior neoadjuvant or adjuvant therapy with a platinum agent or mitomycin and experienced recurrence within 12 months after the end of the platinumbased or mitomycin containing therapy, or received platinum or mitomycin for advanced disease.
3. Patient is concurrently using other anti-cancer therapy.
4. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered to grade 1 or less from major side effects.
5. Patient with presence of CTCAE grade 2 toxicity or higher due to prior cancer therapy.
Exception: Patients with any grade of alopecia are allowed to enter the study.
6. Patient has received radiotherapy = 4 weeks prior to randomization (= 2 weeks for limited field radiation for palliation), and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia).
7. Patient has a known hypersensitivity to other monoclonal antibodies, platinum-containing compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin.
8. Patient with history of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, or a history of severe hypersensitivity reactions, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
9. History of acute pancreatitis within 1 year of screening or past medical history of chronic
pancreatitis.
10. Clinically significant cardiac disease or impaired cardiac function, including any of the following: Cardiac or cardiac repolarization abnormality, including any of the following:
i. History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to randomization
ii. History or current diagnosis of myocarditis
iii. Cardiac troponin T (TnT) or I (TnI) elevated > 2 x ULN at screening. Repeat Troponin test if values are between >1 and 2 x ULN:
- Patients with a screening or repeat levels = 1 x ULN may be included.
- If repeat Troponin levels are > 1 and < 2 x ULN, patient can be included at the investigator’s discretion after cardiac assessment
- Repeat assessment should be performed the following day if possible but may be later.
iv. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) or uncontrolled hypertension
v. QTcF > 470 msec on screening central ECG or long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia
- Concomitant medication(s) known to cause Torsades de Pointe” per www.qtdrugs.org that cannot be discontinued or replaced by safe alternative medication. (within 5 half-lives or 7 days prior to starting study drug)
- Inability to determine the QTcF interval.
Other protocol-defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method