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

SOLTI

Status and phase

Enrolling

Phase 2

Conditions

Breast Cancer

Treatments

Drug: Atezolizumab + Trastuzumab + Vinorelbine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04759248

SOLTI-1907

2020-000245-13 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

55 estimated patients

Sex

All

Ages

18+ years old

Volunteers

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.