Triple Negative Breast Cancer
Conditions
Keywords
Triple Negative Breast Cancer, PD-L1-positive, Locally advanced or metastatic breast cancer
Brief summary
Triple-negative breast cancer (TNBC) is among the most aggressive and lethal types of breast cancer, and currently available therapies have an unsatisfactory impact on patients' survival. The primary aim of this clinical trial is to evaluate efficacy in terms of Overall Response Rate (ORR) of atezolizumab plus cyclophosphamide and vinorelbine in first line patients with unresectable locally advanced or metastatic TNBC patients, previously treated with anti-programmed cell death ligand-1 (PD-L1) or anti-programmed cell death-1 (PD-1) - containing regimens, in the neoadjuvant/adjuvant setting.
Detailed description
TNBC is among the most aggressive and lethal types of breast cancer, and currently available therapies have an unsatisfactory impact on patients' survival. The association of checkpoint inhibitors (CIs) such as anti-PD-L1 with chemotherapy has shown some encouraging results in randomized clinical trials enrolling TNBC patients either in the early (neo-adjuvant) or in the advanced/metastatic setting, but there has been no clear evidence of what should be considered the best chemotherapy backbone to be associated with CIs. What could be considered the most promising combinatorial regimen of chemotherapy plus anti-PDL1 was defined using two complementary TNBC models at the preclinical level. The present phase II study will investigate overall response rate (ORR) as primary endpoint in first line metastatic TNBC patients treated with this investigational combination comprising atezolizumab (A) Vinorelbine (V), and Cyclophosphamide (C). Secondary objectives will investigate duration of response (DOR), progression-free survival (PFS) and overall survival (OS) and the safety of the study regimen.
Interventions
DRUGAtezolizumab in combination with Cyclophosphamide and Vinorelbine
Patients will receive Atezolizumab in combination with Cyclophosphamide and Vinorelbine in 28-day cycles
Sponsors
European Institute of Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, phase II, single arm, multicenter study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * Patients with locally advanced or metastatic, histologically documented TNBC (absence of human epidermal growth factor 2 \[HER2\], estrogen receptor \[ER\], and progesterone receptor \[PR\] expression) PD-L1+ (Immune Cell \>1% using Ventana SP142 assay), not amenable to surgical therapy * Locally advanced or metastatic TNBC, who have received an anti-PD-1/PD-L1 containing regimen in the neoadjuvant/adjuvant setting * No prior chemotherapy or targeted systemic therapy (including endocrine therapy) or immunotherapy for inoperable locally advanced or metastatic TNBC * Tissue accessible for biopsies * Expected survival of \> 3 months * Female or male subject ≥18 years * Have measurable/evaluable metastatic disease (RECIST 1.1 criteria) * Performance status 0-1 on Eastern Cooperative Oncology Group Performance Status (ECOG PS) * Demonstrate adequate organ (kidney, liver) function
Exclusion criteria
* Patients with de novo metastatic TNBC OR those who have received 1 or more chemotherapy or targeted systemic therapy (including endocrine therapy) or immunotherapy regimens for advanced disease * Immunodeficiency or systemic steroid therapy/immunosuppressive therapy within 7 days prior to study entry * Known history of active Bacillus Tuberculosis (TBC) * Hypersensitivity to anti- PD-L1 antibodies or its excipients * Active autoimmune disease * Known history of non-infectious pneumonitis * Active infection requiring systemic therapy * Known history of Human Immunodeficiency Virus (HIV) * Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\]) * Live vaccine within 30 days * Bone or brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 30 months | Rate of subjects who achieve either a confirmed Complete Response (CR) or Partial Response (PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 30 months | Interval from treatment initiation to disease progression or death, whichever comes first, or to the last disease assessment for patients alive without progression |
| Overall survival (OS) | 30 months | Interval from treatment initiation to death or last known alive date |
| Duration on response (DoR) | 30 months | Time between the first documented objective response (CR or PR) and the first documented progression or death due to any cause |
Countries
Italy
Contacts
Primary ContactElisabetta Munzone, MD
Backup ContactMara Negri
Outcome results
None listed