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

NCT04759248

Active Not RecruitingPhase 2

Sponsor: SOLTI Breast Cancer Research Group

Conditions: Breast Cancer

Interventions: Atezolizumab + Trastuzumab + Vinorelbine

Countries: Spain

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

Eligibility overview

Sex: ALL

Age: 18 Years to

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria
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.
Locations (15)
  • Granada, Andalusia, Spain
  • Barcelona, Barcelona, Spain
  • L'Hospitalet de Llobregat, Barcelona, Spain
  • Santa Cruz de Tenerife, Canary Islands, Spain
  • A Coruña, La Coruña, Spain
  • Alicante, Spain
  • Barcelona, Spain
  • Barcelona, Spain
  • Cáceres, Spain
  • León, Spain
  • Madrid, Spain
  • Palma de Mallorca, Spain
  • Reus, Spain
  • Seville, Spain
  • Valencia, Spain