Combination of Atezolizumab, Trastuzumab, and Vinorelbine for HER2-positive Advanced Breast Cancer

A Phase II With 2 Parallel Cohorts Clinical Trial Targeting Estrogen Receptor Negative or PAM50 Non-luminal Disease With Atezolizumab in Combination With Trastuzumab and Vinorelbine in HER2-positive Advanced/Metastatic Breast Cancer - ATREZZO Study

This study is testing if combining three treatments—Atezolizumab, Trastuzumab, and Vinorelbine—can help people with advanced HER2-positive breast cancer feel better and improve their treatment results.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: SOLTI Breast Cancer Research Group (Academic / other)
• Drugs / interventions: trastuzumab, atezolizumab, radiation
• Locations: 15 sites (Granada, Andalucía and 14 other locations)
• Trial ID: NCT04759248 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining Atezolizumab, an immune checkpoint inhibitor, with Trastuzumab and Vinorelbine in patients with HER2-positive advanced or metastatic breast cancer. The study aims to enhance treatment outcomes by leveraging the immune response alongside traditional therapies. Eligible participants must have previously received trastuzumab and other anti-HER2 therapies, and the trial will assess the response based on measurable disease criteria. The approach is based on the understanding that certain breast cancer subtypes may benefit more from this combination due to their immune profile and tumor mutational burden.

Who should consider this trial

Good fit: Ideal candidates include male and female patients with histologically confirmed HER2-positive metastatic breast cancer who have previously received trastuzumab.

Not a fit: Patients with a history of other malignancies in the past three years or those with symptomatic leptomeningeal disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could significantly improve survival rates and quality of life for patients with advanced HER2-positive breast cancer.

How similar studies have performed: Previous studies have shown promising results with similar combination therapies in advanced breast cancer, indicating potential for success in this approach.

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.

Where this trial is running

Granada, Andalucía and 14 other locations

• H. Clínico San Cecilio de Granada — Granada, Andalucía, Spain (Recruiting)
• Institut Català d'Oncologia Hospitalet — Hospitalet de Llobregat, Barcelona, Spain (Recruiting)
• Hospital Universitario de Canarias — Tenerife, Islas Canarias, Spain (Recruiting)
• Complejo Hospitalario Universitario A Coruña (CHUAC) — A Coruña, La Coruña, Spain (Recruiting)
• Hospital General Universitario de Alicante — Alicante, Spain (Recruiting)
• Hospital del Mar — Barcelona, Spain (Recruiting)
• Hospital Clinic de Barcelona — Barcelona, Spain (Recruiting)
• Hospital Universitari Vall d' Hebron — Barcelona, Spain (Recruiting)
• Hospital San Pedro de Alcántara — Cáceres, Spain (Recruiting)
• Hospital de León — León, Spain (Recruiting)
• Hospital Universitario 12 de octubre — Madrid, Spain (Recruiting)
• Hospital Son Espases — Palma De Mallorca, Spain (Recruiting)
• Hospital Universitari Sant Joan de Reus — Reus, Spain (Recruiting)
• Hospital Universitario Virgen del Rocio — Sevilla, Spain (Recruiting)
• Hospital Clinico Universitario de Valencia — Valencia, Spain (Recruiting)

Conditions Breast Cancer; cancer; breast cancer