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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Atezolizumab in combination with Cyclophosphamide and Vinorelbine

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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mara Negri; Phone Number: +39 0257489536; Email: mara.negri@ieo.it
• Study Contact Backup: Name: Elisabetta Munzone, MD; Phone Number: +39 0257489405; Email: elisabetta.munzone@ieo.it

Study Locations

• Italy
  • Brindisi, Italy
    • Not yet recruiting
    • Azienda Sanitaria Locale Br
    • Contact: Saverio Cinieri, MD; Phone Number: 00390831537217; Email: saverio.cinieri@me.com
  • Milan, Italy, 20141
    • Recruiting
    • European Institute of Oncology
    • Contact: Elisabetta Munzone, MD; Phone Number: +39 0257489405; Email: elisabetta.munzone@ieo.it
  • Monza
    • Monza, Monza, Italy, 20900
      • Recruiting
      • Fondazione IRCCS San Gerardo dei Tintori
      • Contact: Maria Elena Cazzaniga, MD; Phone Number: 00390392339037; Email: marina.cazzaniga@irccs-sangerardo.it
  • Roma
    • Roma, Roma, Italy, 00168
      • Not yet recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Contact: Antonella Palazzo, MD; Phone Number: 00390630156318; Email: antonella.palazzo@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab plus Cyclophosphamide and Vinorelbine; Atezolizumab 840 mg intravenous (IV) on Days 1 and 15 of every 28-day cycle in combination with Cyclophosphamide 300 mg/m2 IV on Days 1 ,8,15, 21 of every 28-day cycle and Vinorelbine 30 mg per os (PO) on Days 1, 3, 5 every week of every 28-day cycle	Drug: Atezolizumab in combination with Cyclophosphamide and Vinorelbine; Patients will receive Atezolizumab in combination with Cyclophosphamide and Vinorelbine in 28-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Rate of subjects who achieve either a confirmed Complete Response (CR) or Partial Response (PR)	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Interval from treatment initiation to disease progression or death, whichever comes first, or to the last disease assessment for patients alive without progression	30 months
Overall survival (OS)	Interval from treatment initiation to death or last known alive date	30 months
Duration on response (DoR)	Time between the first documented objective response (CR or PR) and the first documented progression or death due to any cause	30 months

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Principal Investigator: Elisabetta Munzone, MD, European Istitute of Oncology; Principal Investigator: Francesco Bertolini, European Istitute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2025
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: January 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Triple Negative Breast Cancer; Locally advanced or metastatic breast cancer; PD-L1-positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Alkaloids; Indoles; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Vinorelbine; Cyclophosphamide; atezolizumab
• Other Study ID Numbers: UID 2686

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No