Abstract 884TiP
Background
Prognosis of advanced/recurrent endometrial cancer (EC) is poor with median survival of 12-15 months for patients with measurable disease. Among the limited therapeutic options, the primary management is represented by chemotherapy with carboplatin and paclitaxel. EC is known to be one of the tumor types with highest mutation frequency. The two subgroups of ultra- and hyper-mutated EC, which harbor POLE and mismatch repair gene defects respectively, have shown to be associated with higher predicted neoantigen load, peri-tumoral T cell infiltration and high expression of PD-1 and PD-L1 proteins, making EC a good candidate for immune checkpoint inhibitor therapy. Preliminary data in EC have shown promising clinical evidence of tumor response to the PD-L1 targeting agent atezolizumab. This study aims at evaluating the efficacy of first-line atezolizumab versus placebo in combination with carboplatin and paclitaxel.
Trial design
This is a multicenter, phase III, double-blind, randomized trial in patients with newly diagnosed, advanced stage III/IV or recurrent EC. Patients are randomized in a 1:2 ratio into: i. control group receiving standard chemotherapy (175 mg/m2 paclitaxel plus AUC5/6 carboplatin) plus placebo IV every 21 days up to 6/8 cycles followed by placebo until progression; experimental group receiving standard chemotherapy (175 mg/m2 paclitaxel and AUC5/6 carboplatin) plus 1200 mg atezolizumab IV every 21 days up to 6/8 cycles followed by atezolizumab until progression. Stratification factors are: histology, disease stage, microsatellite status, country of experimental site. The trial has two co-primary independent endpoints, PFS and OS. Secondary endpoints include ORR, duration of response, PFS2, quality of life, adverse events and compliance. Further exploratory endpoints relate to prognostic and predictive tumor biomarkers. The study is sponsored by the Italian MaNGO group and is involving sites from ENGOT and GCIG networks across Europe, Japan, Australia and New Zealand. As of May 18th 2020, 182 out of 550 patients have been randomized.
Clinical trial identification
NCT03603184.
Editorial acknowledgement
Legal entity responsible for the study
Mario Negri Gynecology Oncology Group (MaNGO) - Istituto di Ricerche Farmacologiche Mario Negri IRCCS.
Funding
Co-funding no-profit Institution (Istituto di Ricerche Farmacologiche Mario Negri IRCCS) and Pharmaceutical Companies (F. Hoffmann-La Roche Ltd, Chugai Pharmaceutical Co. Ltd).
Disclosure
N. Colombo: Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Clovis; Honoraria (self), Advisory/Consultancy: Tesaro/GSK; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Biocad; Honoraria (self), Advisory/Consultancy: Immunogen; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Advaxis. Y. Antill: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Eisai; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Novartis. M.P. Barretina Ginesta: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: PharmaMar. K. Harano: Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Taiho; Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Chugai. E. Hudson: Advisory/Consultancy: Roche. F. Marmé: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self): Clovis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Tesaro/GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Lilly; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self): Celgene; Honoraria (self): Janssen-Cilag; Honoraria (self), Advisory/Consultancy: GenomicHealth; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Vaccibody; Travel/Accommodation/Expenses: PharmaMar. C. Marth: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: GSK; Research grant/Funding (institution): EU; Research grant/Funding (institution): FWF. A.A. Secord: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy, Research grant/Funding (institution), no honoraria: AstraZeneca; Research grant/Funding (institution): Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Travel/accomadation/expenses to participate on Advisory Board: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Immutep Ltd; Research grant/Funding (institution): Seattle Genetics, Inc; Research grant/Funding (institution), Steering Committee member for AtTEND trial - no honorarium: Roche/Genentech; Research grant/Funding (institution), Steering Committee member for OVAL trial - no honorarium: VBL Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro/GSK; Honoraria (self): Aravive; Honoraria (self): Myriad; Research grant/Funding (institution): National Cancer Trial Network; Officer/Board of Directors: GOG-Foundation Board of Directors. R. Fossati: Research grant/Funding (institution): Tesaro/GSK; Research grant/Funding (institution): Roche; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): AstraZeneca. A. Roberto: Research grant/Funding (institution): Roche; Research grant/Funding (institution): Associazione Italiana per la Ricerca sul Cancro. F. Tettamanzi: Research grant/Funding (institution): Roche; Research grant/Funding (institution): AstraZeneca. E. Biagioli: Research grant/Funding (institution): Tesaro/GSK; Research grant/Funding (self): Roche; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.