Atezolizumab with cyclophosphamide and vinorelbine for metastatic triple-negative breast cancer
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
This trial will test whether adding atezolizumab to the chemotherapy drugs cyclophosphamide and vinorelbine helps people with PD-L1–positive metastatic triple-negative breast cancer who are starting first-line treatment after prior PD-1/PD-L1 therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 45 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | European Institute of Oncology Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, atezolizumab, cyclophosphamide |
| Locations | 5 sites (Monza, Monza and 4 other locations) |
| Trial ID | NCT06690840 on ClinicalTrials.gov |
What this trial studies
This Phase 2 trial gives atezolizumab together with cyclophosphamide and vinorelbine to adults with PD-L1–positive, unresectable locally advanced or metastatic triple-negative breast cancer who have not received prior systemic therapy for metastatic disease but had PD-1/PD-L1 drugs in the neoadjuvant/adjuvant setting. The primary endpoint is overall response rate (ORR) by RECIST 1.1, and secondary endpoints include duration of response, progression-free survival, overall survival, and safety. Eligible patients must have measurable disease, ECOG 0–1, adequate organ function, and tissue accessible for biopsies, with treatment continued until progression or unacceptable toxicity. The regimen was chosen based on complementary preclinical TNBC models aiming to identify an optimal chemotherapy backbone to pair with checkpoint inhibition.
Who should consider this trial
Good fit: Adults (≥18 years) with unresectable locally advanced or metastatic PD-L1–positive (IC >1% by Ventana SP142) triple-negative breast cancer who received prior PD-1/PD-L1 therapy in the neoadjuvant/adjuvant setting, have measurable disease, ECOG 0–1, adequate organ function, and accessible tissue for biopsies are the intended participants.
Not a fit: Patients with PD-L1–negative tumors, those who have already received systemic therapy for metastatic disease, or those with poor performance status or significant organ dysfunction are unlikely to benefit from this regimen.
Why it matters
Potential benefit: If successful, this combination could increase tumor response rates and prolong the time patients live without disease progression compared with current options.
How similar studies have performed: Previous randomized trials combining anti–PD-1/PD-L1 agents with chemotherapy in TNBC have shown benefit in some settings (for example atezolizumab plus nab‑paclitaxel in PD-L1–positive patients) but results have been mixed and the optimal chemotherapy partner remains uncertain.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Monza, Monza and 4 other locations
- Fondazione IRCCS San Gerardo Dei Tintori — Monza, Monza, Italy (Recruiting)
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma, Roma, Italy (Not_yet_recruiting)
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma, Roma, Italy (Not_yet_recruiting)
- Azienda Sanitaria Locale Br — Brindisi, Italy (Not_yet_recruiting)
- European Institute of Oncology — Milan, Italy (Recruiting)
Study contacts
- Principal investigator: Elisabetta Munzone, MD — European Istitute of Oncology
- Study coordinator: Elisabetta Munzone, MD
- Email: elisabetta.munzone@ieo.it
- Phone: +39 0257489405
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.