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

NCT04759248 | Active Not Recruiting Phase 2

• 2 other identifiers: SOLTI-19072020-000245-13
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 15

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

Keywords

cancer; breast cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response rate

  the proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

  until disease progression or up to 2 years after treatment ends

Secondary Outcomes (11)

• Overall Response rate in PD-L1+ patients

  until disease progression or up to 2 years after treatment ends

• Clinical Benefit

  24 weeks

• Overal survival

  Until analysis data cutoff, 2 years

• Progression free survival

  24 weeks

• Duration of response

  24 weeks

Study Arms (1)

Atezolizumab in combination with Trastuzumab and Vinorelbine

EXPERIMENTAL

Drug: Atezolizumab + Trastuzumab + Vinorelbine

Interventions

Atezolizumab + Trastuzumab + Vinorelbine 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.

Atezolizumab in combination with Trastuzumab and Vinorelbine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Roche Pharma AG: collaborator

Study Sites (15)

H. Clínico San Cecilio de Granada

Granada, Andalusia, Spain

Location

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

Location

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, 38320, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, La Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d' Hebron

Barcelona, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, Spain

Location

Hospital de León

León, 24071, Spain

Location

Hospital Universitario 12 de octubre

Madrid, Spain

Location

Hospital Son Espases

Palma de Mallorca, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, 43201, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

atezolizumab; Trastuzumab; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, single arm, Simon 2-stage, multicenter phase II study evaluating treatment with atezolizumab in combination with trastuzumab and vinorelbine in patients with locally advanced or metastatic PAM50 non-luminal/HER2+ BC refractory to trastuzumab based therapy and anti-HER2 ADC treatment.

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 18, 2021
• Study Start: March 15, 2021
• Primary Completion: December 1, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)