LAUSR

Abstract Background Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. On March 8th 2019, the Food and Drug Administration approved anti–PD-L1 antibody, atezolizumab, in combination with chemotherapy for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC. Trial design ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated May 4th 2018, and approximately 430 sites are expected to open globally in 30 countries. This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinical trial identification NCT03498716. Legal entity responsible for the study This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Funding Roche. Disclosure M. Ignatiadis: Advisory / Consultancy: Celgene, Novartis, Pfizer, Seattle Genetics, Tesaro; Research grant / Funding (institution): Roche, Menarini Silicon Biosystems, Janssen Diagnostics, Pfizer; Travel / Accommodation / Expenses: Pfizer,Bayer. H.L. McArthur: Advisory / Consultancy: LIlly, Amgen, Immunomedics, Pfizer, Genentech, BMS, Genomic Health, Merck, spectrum pharmaceuticals; Research grant / Funding (institution): BMS, Lilly, Merck, Ziopharm Oncology. J. Martinez: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.. C. Lai: Full / Part-time employment: Roche/Genentech; Shareholder / Stockholder / Stock options: Roche/Genentech. T. Goulioti: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.; Shareholder / Stockholder / Stock options: GlaxoSmithKline; Spouse / Financial dependant: GlaxoSmithKline, UCB. A. Bouhlel: Full / Part-time employment: Roche. V. Balta: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.. G. Viale: Honoraria (self): MSD Oncology; Advisory / Consultancy: Dako, Roche/genentech, Astellas Pharma, Novartis; Research grant / Funding (self): Roche/genentech; Research grant / Funding (institution): Ventana Medical Systems, Dako/Agilent Technologies; Travel / Accommodation / Expenses: Roche, Celgene. D.A. Nguyen: Shareholder / Stockholder / Stock options: Roche/Genentech; Full / Part-time employment: Roche/Genentech. R.D. Gelber: Research grant / Funding (institution): Roche, Novartis, Pfizer, Merck, Celgene, Ferring, Ipsen, AstraZeneca. M. Piccart: Officer / Board of Directors: Radius; Advisory / Consultancy: AstraZeneca, Lilly, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Camel-IDS, Crescendo Biologics, Periphagen, Huya, Debiopharm, PharmaMar, G1 Therapeutics, Menarini, Seattle Genetics, Immunomedics, Oncolytics; Research grant / Funding (institution): AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche-Genentech, Synthon, Radius, Servier. E.P. Winer: Honoraria (self): Genentech, Leap, Carrick Therapeutics, Lilly, Seattle Genetics, GSK. All other authors have declared no conflicts of interest.