Study With Atezolizumab in Combination With Trastuzumab and Vinorelbine in HER2-positive Advanced/Metastatic Breast Cancer (ATREZZO)



Status and phase

Phase 2


Breast Cancer


Drug: Atezolizumab + Trastuzumab + Vinorelbine

Study type


Funder types



2020-000245-13 (EudraCT Number)

Details and patient eligibility


Immune checkpoint inhibitors given in monotherapy in advanced breast cancer have shown modest benefit in first-line, but very limited efficacy in later lines. Thus, combination therapies are needed.

Response following anti-PD1/PD-L1 monotherapy is associated with large survival benefit in the advanced setting.

Previous studies of the intrinsic subtypes have shown that Basal-like and HER2-E are associated with higher expression of immune-related genes or higher infiltration of stromal tumor infiltrating lymphocytes compared to the luminal subtypes. Immune infiltration in BC is associated with chemo/antiHER2 responsiveness and potentially benefit from anti-PD-1/PD-L1 inhibitors.

In addition, one emerging biomarker of response to anti-PD-1 therapy is the tumor mutational burden (I.e. the total number of mutations per coding area of a tumor genome). The HER2-E and Basal-like profiles have been associated with high mutational burden.

A range of studies have been initiated including several phase II/III studies evaluating atezolizumab in combination with different chemotherapeutic compounds routinely used in breast cancer, but none with predefined biomarker beyond the expression of PD-L1 by IHC


55 estimated patients




18+ years old


No Healthy Volunteers

Inclusion criteria

  • Male or female (Premenopausal or postmenopausal women)
  • ECOG 0 to 2
  • Histologically confirmed adenocarcinoma of the breast, metastatic or unresectable locally advanced.
  • All patients must have received at least trastuzumab and other anti-HER2 ADCs (including but not limited to T-DM1).
  • Measurable disease according to RECIST 1.1 criteria.
  • Adequate organ function
  • Baseline LVEF ≥50%
  • Participants with asymptomatic brain metastases are eligible.

Exclusion criteria

  • Treatment with any investigational anticancer drug within 14 days of the start of study treatment.
  • Patient has received Vinorelbine or any other vinca alkaloids previously immediately prior to initiate study treatment.
  • History of other malignant tumors in the past 3 years
  • Known or suspected leptomeningeal disease (LMD)/ poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases.
  • Symptomatic hypercalcemia requiring treatment with bisphosphonates in the 14 days prior to inclusion
  • Cardiopulmonary dysfunction
  • Any other severe, uncontrolled
  • Major surgery in the 28 days prior to enrolment
  • Infection with HIV or active Hepatitis B and/or Hepatitis C.
  • History of trastuzumab intolerance, including grade 3-4 infusion reaction or hypersensitivity.
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History of autoimmune disease,
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. (Note: History of radiation pneumonitis in the radiation field [fibrosis] is permitted.)
  • Active tuberculosis
  • Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment
  • Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or immune checkpoint targeting agents
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug prior to enrolment
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to enrolment, or anticipated requirement for systemic immunosuppressive medications during the trial.

Trial design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

55 participants in 1 patient group

Atezolizumab in combination with Trastuzumab and Vinorelbine
Experimental group
Drug: Atezolizumab + Trastuzumab + Vinorelbine

Trial contacts and locations



Data sourced from

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