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

• Status: Recruiting
• Trial end date: 2025-02-24
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: SOLTI Breast Cancer Research Group
• Collaborator: Roche Pharma AG
• Treatments: Atezolizumab; Trastuzumab; Vinorelbine

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 pertuzumab/trastuzumab and T-DM1

• Measurable disease according to RECIST 1.1 criteria.

• Adequate organ function

• Baseline LVEF ≥50%

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.

• History of other malignant tumors in the past 3 years

• 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.