Thero2-01S22 in HER2-positive Breast Cancer

Trastuzumab and pertuzumab based regimen are the standard of care for patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC), significantly improving survival outcomes. However, an unmet medical need remain for patients with disease refractoriness and recurrence. Interestingly, HER2 over-expression is associated with upregulation of vascular endothelial growth factor (VEGF) in cancer cells in vitro and in vivo. Preclinical studies indicated that VEGF expression is positively regulated by HER2 signaling. In the clinical setting, HER2 over-expression correlated significantly with VEGF over- expression in samples from patients with breast cancer. There is, therefore, a biologic rationale for targeting both HER2 and VEGF pathways in patients with HER2-positive breast cancer.PURPOSE: The hypothesis that justifies this research is that the addition of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment will improve the efficacy of anti-HER2 targeted containing regimen at the metastatic setting for breast cancer.

Inclusion Criteria:Women aged > 18Metastatic setting of an histologically confirmed adenocarcinoma of the breastPerformance status = 0, 1 or 2Metastatic disease requiring the initiation of an anti HER2 containing regimenFirst line treatment for metastatic diseaseStandard treatment including Trastuzumab and Pertuzumab in first linePatients for whom a 3-month life expectancy is anticipatedBaseline LVEF value > 50%, measured cardiac MRI or by echocardiography (Simpson's method) or MUGA scan within 12 weeks before initiation of the treatment. According to HERCEPTIN SPCs.Overexpression of HER2 in the invasive component of the primary tumor (3+ by ICH or 2+ with confirmation of positivity by FISH or CISH)Informed consent form signedExclusion Criteria:Patients not eligible for anti-HER2 therapyPatients previously treated at the metastatic setting by systemic treatmentSerious cardiac illness or medical conditions disallowing administration of anti-HER2 therapy. According to HERCEPTIN and PERJETA SPCs.Known hypersensitivity to trastuzumab, pertuzumab, Thero2-01S22, murine proteins or to any of the excipients.Uncontrolled central nervous system metastatic lesionPatients who, for social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controlsPregnant or breastfeeding women