Study With Atezolizumab in Combination With Trastuzumab and Vinorelbine in HER2-positive Advanced/Metastatic Breast Cancer
- Registration Number
- NCT04759248
- Lead Sponsor
- SOLTI Breast Cancer Research Group
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 55
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Atezolizumab in combination with Trastuzumab and Vinorelbine Atezolizumab + Trastuzumab + Vinorelbine -
- Primary Outcome Measures
Name Time Method Overall Response rate until disease progression or up to 2 years after treatment ends 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
- Secondary Outcome Measures
Name Time Method Overall Response rate in PD-L1+ patients until disease progression or up to 2 years after treatment ends 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
Progression free survival 24 weeks Survival witouth observed progression
Overall Response rate in patients with brain metastases at baseline Until disease progression or up to 2 years after treatment ends Patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline
Clinical Benefit in patients with brain metastases at baseline 24 weeks Clinical Benefit Rate at 24 weeks in patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline
Clinical Benefit 24 weeks Clinical Benefit Rate at 24 weeks
Time to response 24 weeks time until first documented response
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] until end of treatment / through study completion, an average of 1 year AEs according to CTCAE v 5.0.
Overal survival in patients with brain metastases at baseline Until analysis data cutoff, 2 years Time from the date of allocation to the date of death due to any cause.
Overal survival Until analysis data cutoff, 2 years Time from the date of allocation to the date of death due to any cause.
Duration of response 24 weeks time from first documented response until progression
Progression free survival in patients with brain metastases at baseline 24 weeks Survival without observed progression in patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline
Trial Locations
- Locations (15)
Hospital Universitario 12 de octubre
🇪🇸Madrid, Spain
H. Clínico San Cecilio de Granada
🇪🇸Granada, Andalucía, Spain
Institut Català d'Oncologia Hospitalet
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸A Coruña, La Coruña, Spain
Hospital Universitario de Canarias
🇪🇸Tenerife, Islas Canarias, Spain
Hospital Universitari Vall d' Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital Son Espases
🇪🇸Palma De Mallorca, Spain
Hospital de León
🇪🇸León, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari Sant Joan de Reus
🇪🇸Reus, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain