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

NCT ID: NCT04759248

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-15
• Study Completion Date: 2027-07-01

Brief 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

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab in combination with Trastuzumab and Vinorelbine

Group Type: EXPERIMENTAL

Atezolizumab + Trastuzumab + Vinorelbine

Intervention Type: DRUG

• Atezolizumab IV 1200 mg in combination with
• Trastuzumab sc 600mg or IV 6mg/kg every 3 weeks and
• Vinorelbine 25 mg/m² IV or 60 mg/m2 PO on days 1 and 8, every 3 weeks during the first cycle and if there are no toxicity signs dose will be increased to 80 mg/m2 PO o 30 mg/m2 IV.

Interventions

Atezolizumab + Trastuzumab + Vinorelbine

• Atezolizumab IV 1200 mg in combination with
• Trastuzumab sc 600mg or IV 6mg/kg every 3 weeks and
• Vinorelbine 25 mg/m² IV or 60 mg/m2 PO on days 1 and 8, every 3 weeks during the first cycle and if there are no toxicity signs dose will be increased to 80 mg/m2 PO o 30 mg/m2 IV.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

SOLTI Breast Cancer Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

H. Clínico San Cecilio de Granada

Granada, Andalusia, Spain

Hospital del Mar

Barcelona, Barcelona, Spain

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, Spain

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, La Coruña, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitari Vall d' Hebron

Barcelona, , Spain

Hospital San Pedro de Alcántara

Cáceres, , Spain

Hospital de León

León, , Spain

Hospital Universitario 12 de octubre

Madrid, , Spain

Hospital Son Espases

Palma de Mallorca, , Spain

Hospital Universitari Sant Joan de Reus

Reus, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Countries

Spain

Other Identifiers

2020-000245-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SOLTI-1907

Identifier Type: -

Identifier Source: org_study_id