triple negative breast cancer MedDRA version: 20.0 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient has advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) breast cancer. • 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) • 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 • Patient must have received prior systemic treatment that included taxane-based chemotherapy for adjuvant or metastatic disease • 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. • 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 =65 years) yes F.1.3.1 Number of subjects for this age range 59
Exclusion criteria
Exclusion criteria: • 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). • Patient received prior neoadjuvant or adjuvant therapy with a platinum agent or mitomycin and experienced recurrence within 12 months after the end of the platinum-based or mitomycin containing therapy, or received platinum or mitomycin for advanced disease. • 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. • 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. • 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). • Patient has a known hypersensitivity to other monoclonal antibodies, platinumcontaining compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin. • Patient with history or presence of central nervous system (CNS) metastases, treated or untreated. Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the antitumor activity of the three treatment arms LAG525 + spartalizumab, LAG525 + spartalizumab + carboplatin and LAG525 + carboplatin, in subjects with advanced TNBC in first or second line therapy, as measured by the overall response rate (ORR) per investigator's assessment according to RECIST v1.1;Secondary Objective: - To assess the efficacy of the three treatment arms with respect to DOR per investigator’s assessment according to RECIST v1.1 - To assess Overall Survival for each treatment arm - To characterize the PK parameter, Ctrough, of LAG525, spartalizumab, and carboplatin in the three investigated combinations - To assess the efficacy of the three treatment arms with respect to TTR per investigator’s assessment according to RECIST v1.1 - To assess the efficacy of the three treatment arms with respect to PFS per investigator’s assessment according to RECIST v1.1 - To assess the efficacy of the three treatment arms with respect to CBR per investigator’s assessment according to RECIST v1.1 - To characterize the PK parameter, Cmax, of LAG525, spartalizumab, and carboplatin in the three investigated combinations - To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations;Primary end point(s): Overall response rate (ORR) per RECIST v1.1 per investigators'assessment;Timepoint(s) of evaluation of this end point: Every 6 weeks for the first 6 months and every 12 weeks thereafter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Duration of response (DOR) 2) Overall Survival (OS) 3) Pharmacokinetics (PK) parameter, Ctrough, of LAG525, spartalizumab and carboplatin 4) Time to response (TTR) 5) Progression free survival (PFS) 6) Clinical Benefit Rate (CBR) 7) PK parameter, Cmax of LAG525, spartalizumab and carboplatin 8) Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment for LAG525 and spartalizumab;Timepoint(s) of evaluation of this end point: - Every 6 weeks for the first 6 months and every 12 weeks thereafter 1) Every 12 weeks until death, lost to follow-up, or withdrawal of consent 2) From cycle 1 to cycle 7 and at EOT with more timepoints at C1 and C3 3, 4 & 5) Every 6 weeks for the first 6 months and every 12 weeks thereafter 6) From cycle 1 to cycle 7 and at EOT with more timepoints at C1 and C3 7) At Day 1 of each cycle until cycle 7 and at EOT | — |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Lebanon, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed