Abstract 354TiP
Background
T-DM1 is the standard second-line treatment for HER2-positive Metastatic Breast Cancer (HER2+ MBC) patients. In clinical practice, it is not possible to predict which patients will benefit the most from T-DM1. Furthermore, the mechanisms of primary and acquired resistance to T-DM1 remain largely uncharacterized. The task of uncovering such mechanisms in a clinical setting is challenging and requires a comprehensive approach.
Trial design
This is a prospective, multicenter study in HER2+ MBC patients planned to be treated with T-DM1 according to the Standards of Care (3,6 mg/kg IV every 3 weeks). Patients must have previous treatment with trastuzumab and taxanes, either prior therapy for MBC or recurrence during or within six months of completing adjuvant therapy, and measurable disease according to RECIST 1.1. Sequential tumor, plasma and serum samples are collected. A comprehensive genomic profiling of tumor and liquid biopsies will be performed using the Foundation-One and Foundation-Act assays (Foundation Medicine), respectively. Additionally, we will explore on pretreatment and progression tumor samples the intra and inter-tumor heterogeneity of HER2 expression, Cyclin B1 status, tumor immune microenvironment (PD-L1, tumor-infiltrating lymphocytes), gene expression patterns and tumor subtypes. Furthermore, we will detect HER2 amplification and explore dynamics on circulating tumor DNA. The primary objective is the biomarkers correlation with objective response to T-DM1. The secondary objectives are: biomarkers correlation with progression-free survival (PFS) at 6 and 12 months; biomarkers correlation with PFS and Time to Progression as continuous variables; and to assess safety and tolerability This study will be opened for recruitment for approximately 30 months (Oct 2018-Mar 2021). Patients will be followed for at least 12 months since the last patient has been included in the study. Recruitment started in Oct 2018 with 18 pts included up to 31st March 2020. Analysis of the primary endpoint is planned for Q4 2022.
Clinical trial identification
NCT03829306.
Editorial acknowledgement
Legal entity responsible for the study
GEICAM Spanish Breast Cancer Group.
Funding
Roche.
Disclosure
F. Rojo Todo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Archer; Advisory/Consultancy: Pierre Fabre. A. Stradella: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Eisai; Travel/Accommodation/Expenses: Pfizer. J.A. García-Sáenz: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Celgene; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. B. Bermejo De Las Heras: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: MSD; Travel/Accommodation/Expenses: Pfizer. E. Alba: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Lilly; Advisory/Consultancy: BMS; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Research grant/Funding (institution): Nanostring; Travel/Accommodation/Expenses: Celgene; Research grant/Funding (institution): Sysmex; Research grant/Funding (institution): MSD. S. López-Tarruella: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Eisai; Travel/Accommodation/Expenses: MSD. E. Carrasco: Shareholder/Stockholder/Stock options: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, An Immediate Family Member: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, An Immediate Family Member: Novartis; Advisory/Consultancy, An Immediate Family Member: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses, An Immediate Family Member: Roche; Advisory/Consultancy, Research grant/Funding (institution), An Immediate Family Member: Janssen; Advisory/Consultancy, An Immediate Family Member: Amgen; Advisory/Consultancy, Research grant/Funding (institution), An Immediate Family Member: Pfizer; Advisory/Consultancy, An Immediate Family Member: Incyte; Advisory/Consultancy, Research grant/Funding (institution), An Immediate Family Member: AbbVie; Research grant/Funding (institution), An Immediate Family Member: Roche/Genentech; Research grant/Funding (institution), Travel/Accommodation/Expenses, An Immediate Family Member: Celgene; Research grant/Funding (institution): AstraZeneca Spain; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): AstraZeneca; Licensing/Royalties: PAM 50 taxane predictor. M. Del Campo: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly. All other authors have declared no conflicts of interest.