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

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

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

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Atezolizumab + Trastuzumab + Vinorelbine

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Recruiting
    • Hospital General Universitario de Alicante
    • Principal Investigator: José Juan Ponce Lorenzo
    • Contact: Juan José Ponce Lorenzo; Phone Number: +34 965 93 30 00
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital Del Mar
    • Contact: Sonia Servitja Tormo; Phone Number: +34 932 48 30 00
    • Principal Investigator: Sonia Servitja Tormo, MD
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic de Barcelona
    • Contact: Olga Martinez; Phone Number: +34 932 27 54 00
    • Principal Investigator: Olga Martínez, MD
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d' Hebron
    • Contact: Santiago Escrivá; Phone Number: +34 934 89 30 00
    • Principal Investigator: Santiago Escrivá, MD
  • Cáceres, Spain
    • Recruiting
    • Hospital San Pedro de Alcántara
    • Principal Investigator: Santiago González, MD
    • Contact: Santiago Gonzalez; Phone Number: +34 927 25 62 00
  • León, Spain, 24071
    • Recruiting
    • Hospital de Leon
    • Principal Investigator: Ana López, MD
    • Contact: Ana Lopez; Phone Number: +34 987 23 74 00
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Principal Investigator: Eva Ciruelos, MD
    • Contact: Eva Ciruelos; Phone Number: +34 91 390 86 26
  • Palma De Mallorca, Spain
    • Recruiting
    • Hospital Son Espases
    • Principal Investigator: Antonia Perelló, MD
    • Contact: Antonia Perelló; Phone Number: +34 871 20 50 00
  • Reus, Spain, 43201
    • Recruiting
    • Hospital Universitari Sant Joan de Reus
    • Contact: Cinta Albacar; Phone Number: +34 977 31 03 00
    • Principal Investigator: Cinta Albacar, MD
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: Javier Salvador Bonfill; Phone Number: +34 955 01 20 00
    • Principal Investigator: Javier Salvador Bonfill, MD
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico Universitario de Valencia
    • Contact: Juan Miguel Cejalvo; Phone Number: +34 961 97 35 00
    • Principal Investigator: Juan Miguel Cejalvo, MD
  • Andalucía
    • Granada, Andalucía, Spain
      • Recruiting
      • H. Clínico San Cecilio de Granada
      • Principal Investigator: Isabel Blancas, MD
      • Contact: Isabel Blancas; Phone Number: +34 958 02 30 00
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain
      • Recruiting
      • Institut Catala d'Oncologia Hospitalet
      • Principal Investigator: Sonia Pernas, MD
      • Contact: Sonia Pernas; Phone Number: +34 932 60 77 33
  • Islas Canarias
    • Tenerife, Islas Canarias, Spain, 38320
      • Recruiting
      • Hospital Universitario de Canarias
      • Contact: Josefina Cruz Jurado; Phone Number: +34 922 67 80 00
      • Principal Investigator: Josefina Cruz Jurado, MD
  • La Coruña
    • A Coruña, La Coruña, Spain, 15006
      • Recruiting
      • Complejo Hospitalario Universitario A Coruña (CHUAC)
      • Contact: María E Perez López; Phone Number: +34 981 178 000
      • Principal Investigator: Maria E Perez López, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab in combination with Trastuzumab and Vinorelbine	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response rate in PD-L1+ patients	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
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	AEs according to CTCAE v 5.0.	until end of treatment / through study completion, an average of 1 year
Overall Response rate in patients with brain metastases at baseline	Patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline	Until disease progression or up to 2 years after treatment ends
Clinical Benefit in patients with brain metastases at baseline	Clinical Benefit Rate at 24 weeks in patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline	24 weeks
Progression free survival in patients with brain metastases at baseline	Survival without observed progression in patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline	24 weeks
Overal survival in patients with brain metastases at baseline	Time from the date of allocation to the date of death due to any cause.	Until analysis data cutoff, 2 years
Clinical Benefit	Clinical Benefit Rate at 24 weeks	24 weeks
Overal survival	Time from the date of allocation to the date of death due to any cause.	Until analysis data cutoff, 2 years
Progression free survival	Survival witouth observed progression	24 weeks
Duration of response	time from first documented response until progression	24 weeks
Time to response	time until first documented response	24 weeks

Collaborators and Investigators

• Sponsor: SOLTI Breast Cancer Research Group
• Collaborators: Roche Pharma AG

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Trastuzumab; Vinorelbine; Atezolizumab
• Other Study ID Numbers: SOLTI-1907; 2020-000245-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No