Atezolizumab and Chemotherapy Treatment as T-cell Activators in Metastatic Triple Negative Breast Cancer Patients

Official title

A Phase II Study of Atezolizumab, Vinorelbine and Weekly Cyclophosphamide as T-cell Activators in First Line Metastatic Triple Negative Breast Cancer Patients Pre-treated With Anti-PD-L1/PD-1

Overview

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

• Drug Atezolizumab in combination with Cyclophosphamide and Vinorelbine
  Patients will receive Atezolizumab in combination with Cyclophosphamide and Vinorelbine in 28-day cycles

Primary outcome measures

• Overall Response Rate (ORR) [Time frame: 30 months]

Secondary outcome measures (3)

• Progression-free survival (PFS) [Time frame: 30 months]
• Overall survival (OS) [Time frame: 30 months]
• Duration on response (DoR) [Time frame: 30 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 5 centers

• Fondazione IRCCS San Gerardo Dei Tintori — Monza
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• Azienda Sanitaria Locale Br — Brindisi
• European Institute of Oncology — Milan

Identifiers

NCT: NCT06690840 · UID 2686

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗