Abstract OT1-08-09: CONTESSA: A multinational, multicenter, randomized, phase 3 registration study of tesetaxel plus a reduced dose of capecitabine in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane
Authors: O'Shaughnessy Joyce , Piccart Martine , Schwartzberg Lee , Cortes Javier , Harbeck Nadia , Im Seock-Ah , Rugo Hope , Untch Michael , Yardley Denise , Bondarenko Igor , Dieras Veronique , Pegram Mark , Kroll Stew , O'Connell Joseph , Vacirca Jeff , Wei Thomas , Tang Kevin , Seidman Andrew 
Published: March 2020

Abstract
Background: Chemotherapy treatments with robust efficacy that preserve quality of life are needed. Tesetaxel is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; preclinical evidence of central nervous system (CNS) penetration; and improved activity against chemotherapy-resistant tumors. More than 600 patients have been treated with tesetaxel in clinical studies. Tesetaxel had robust monotherapy activity in a Phase 2 study in 38 patients with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45% and median PFS of 5.4 months. The confirmed ORR in taxane-pretreated patients also was 45%. Preclinical and clinical studies suggest that reducing the dose of capecitabine in combination with a taxane may result in reduced toxicity without a reduction in efficacy. CONTESSA investigates tesetaxel plus a reduced dose of capecitabine as an all-oral regimen in patients with HER2-, HR+ MBC.
Trial design: CONTESSA is a 600-patient, multinational, multicenter, randomized (1:1), Phase 3 registration study comparing tesetaxel (27 mg/m2 on Day 1 of a 21-day cycle) plus a reduced dose of capecitabine (1,650 mg/m2/day on Days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day on Days 1-14 of a 21-day cycle) in patients with HER2-, HR+ MBC who have received no more than one chemotherapy regimen for advanced disease and have received a taxane in the (neo)adjuvant setting. Patients with known CNS metastases are eligible. The primary endpoint is progression-free survival (PFS) assessed by an Independent Radiologic Review Committee (IRC). CONTESSA is 90% powered to detect a 42% improvement in PFS (HR = 0.71). Secondary endpoints are overall survival, ORR and disease control rate. Enrollment began in December 2017. In June 2019, the Independent Data Monitoring Committee for CONTESSA recommended that the study continue with no modifications following a planned interim efficacy futility analysis. The interim efficacy futility analysis was based on a pre-specified analysis of the first approximate 100 PFS events that occurred in the study. For further information on this trial, email joconnell@odonate.com or visit clinicaltrials.gov (NCT03326674).
Citation Format: Joyce O'Shaughnessy, Martine Piccart, Lee Schwartzberg, Javier Cortes, Nadia Harbeck, Seock-Ah Im, Hope Rugo, Michael Untch, Denise Yardley, Igor Bondarenko, Veronique Dieras, Mark Pegram, Stew Kroll, Joseph O'Connell, Jeff Vacirca, Thomas Wei, Kevin Tang, Andrew Seidman. CONTESSA: A multinational, multicenter, randomized, phase 3 registration study of tesetaxel plus a reduced dose of capecitabine in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-09.