Combination of Talimogene Laherparepvec With Atezolizumab in Early Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Biological: Talimogene laherparepvec
- Registration Number
- NCT03802604
- Lead Sponsor
- SOLTI Breast Cancer Research Group
- Brief Summary
PROMETEO is a window opportunity, single arm, exploratory study to evaluate the effect of T- VEC combined with Atezolizumab in women with operable early breast cancer who present residual disease after Neoadjuvant Chemotherapy (NAC). Other eligibility criteria include TNBC or LumB like primary tumor sized at least 1.5 cm, ECOG PS 0-1 and evaluable diagnostic tumor sample.
- Detailed Description
Primary objective:
• To evaluate the efficacy (as measured by residual cancer burden \[RCB\] class 0/1 rate) of Talimogene Laherparepvec with Atezolizumab given to subjects with operable early breast cancer who present residual disease after neoadjuvant chemotherapy (NAC).
Secondary objectives include:
* To assess the rate of pathological complete response (pCR) in the breast (pCRB) and breast and axilla (pCRBL) at definitive surgery after neoadjuvant treatment with T-VEC and atezolizumab.
* To determine the clinical and radiological ORR of breast tumors to TVEC- atezolizumab given in the neoadjuvant setting.
* To assess RCB index in continuous variable and by the 4 RCB class (RCB0, RCB1, RCB2 and RCB 3) after treatment with T-VEC and atezolizumab.
* Comparing the expression of a gene signature tracking activated CD8 T-cells at surgery after treatment with T-VEC and atezolizumab with residual disease after NAC.
* To evaluate the safety of T-VEC in combination with atezolizumab as assessed by incidence of treatment-emergent and treatment-related adverse events.
* Translational and exploratory objectives are included.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Talimogene laherparepvec + Atezolizumab Talimogene laherparepvec 1. Talimogene laherparepvec: Cycle 1 - 10\^6 PFU/mL. Cycle 2, 3, 4 \& 5 - 10\^8 PFU/mL. 2. Atezolizumab 840 mg Talimogene laherparepvec + Atezolizumab Atezolizumab 1. Talimogene laherparepvec: Cycle 1 - 10\^6 PFU/mL. Cycle 2, 3, 4 \& 5 - 10\^8 PFU/mL. 2. Atezolizumab 840 mg
- Primary Outcome Measures
Name Time Method Rate of residual cancer burden class 0 and 1 (RCB0/1) 24 months since first patient in As a dichotomous measure of tumor response, RCB 0/1 yes vs. no., after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment.
- Secondary Outcome Measures
Name Time Method Tumor ORR 24 months since first patient in Defined as the sum of PR and CR according to RECIST v1.1, as per Investigator's assessments by breast MRI.
Rate of residual cancer burden (RCB) 24 months since first patient in As a continuous variable and by RCB group, after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment.
Changes in the expression of a gene signature tracking activated CD8 T-cells. 24 months since first patient in Differences in in the mean expression of an immune gene signature tracking CD8 T-cells (composed of the following genes: PRF1, CD8A, GZMM, CD8B, FLT3LG) in all patients will be assessed.
Rate of pCRB (ypT0/Tis) and pCRBL (ypT0/TisypN0) 24 months since first patient in Complete absence of invasive carcinoma in the breast or in the breast and axillary lymph nodes on histological examination at the time of definitive surgery, irrespective of in situ carcinoma in the breast and in the breast and axilla by local evaluation will be assessed.
Incidence, duration and severity of AEs assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 4 24 months since first patient in Incidence, duration and severity of AEs assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 4, including delays and treatment discontinuations.
Trial Locations
- Locations (4)
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Clínico universitario de Valencia
🇪🇸Valencia, Spain
Centro Integral Oncológico Clara Campal
🇪🇸Madrid, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain