ATREZZO: Study With Atezolizumab in Combination With Trastuzumab and Vinorelbine in HER2-positive Advanced/Metastatic Breast Cancer
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 |
---|---|---|
|
Phase 2 |
Study Design
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
- 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
- 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
- Clinical Benefit in each cohort [24 weeks]
Clinical Benefit Rate at 24 weeks
- 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.
- Progression free survival in each cohort [24 weeks]
Survival witouth observed progression
- Duration of response in each cohort [24 weeks]
time from first documented response until progression
- Time to response in each cohort [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.
- 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
- 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
- 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
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.- SOLTI-1907
- 2020-000245-13