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

Sponsor
SOLTI Breast Cancer Research Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT04759248
Collaborator
Roche Pharma AG (Industry)
110
15
1
47.4
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Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Atezolizumab + Trastuzumab + Vinorelbine
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
110 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This is an open-label, single arm, Simon 2-stage, multicenter phase II with 2 cohorts 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/Pertuzumab based therapy and T-DM1.This is an open-label, single arm, Simon 2-stage, multicenter phase II with 2 cohorts 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/Pertuzumab based therapy and T-DM1.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Mar 15, 2021
Anticipated Primary Completion Date :
Feb 24, 2023
Anticipated Study Completion Date :
Feb 24, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 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

Secondary Outcome Measures

  1. Overall Response rate in PD-L1-neg 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

  2. Clinical Benefit in each cohort [24 weeks]

    Clinical Benefit Rate at 24 weeks

  3. Overal survival in each cohort [Until analysis data cutoff, 2 years]

    Time from the date of allocation to the date of death due to any cause.

  4. Progression free survival in each cohort [24 weeks]

    Survival witouth observed progression

  5. Duration of response in each cohort [24 weeks]

    time from first documented response until progression

  6. Time to response in each cohort [24 weeks]

    time until first documented response

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 pertuzumab/trastuzumab and 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 H. Clínico San Cecilio de Granada Granada Andalucía Spain
2 Institut Català d'Oncologia Hospitalet Hospitalet de Llobregat Barcelona Spain
3 Hospital Universitario de Canarias Tenerife Islas Canarias Spain 38320
4 Complejo Hospitalario Universitario A Coruña (CHUAC) A Coruña La Coruña Spain 15006
5 Hospital General Universitario de Alicante Alicante Spain
6 Hospital del Mar Barcelona Spain 08003
7 Hospital Clinic de Barcelona Barcelona Spain
8 Hospital Universitari Vall d' Hebron Barcelona Spain
9 Hospital San Pedro de Alcántara Cáceres Spain
10 Hospital de León León Spain 24071
11 Hospital Universitario 12 de octubre Madrid Spain
12 Hospital Son Espases Palma De Mallorca Spain
13 Hospital Universitari Sant Joan de Reus Reus Spain 43201
14 Hospital Universitario Virgen del Rocio Sevilla Spain
15 Hospital Clinico Universitario de Valencia Valencia Spain

Sponsors and Collaborators

  • SOLTI Breast Cancer Research Group
  • Roche Pharma AG

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT04759248
Other Study ID Numbers:
  • SOLTI-1907
  • 2020-000245-13
First Posted:
Feb 18, 2021
Last Update Posted:
Mar 17, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by SOLTI Breast Cancer Research Group
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 17, 2022