CONTESSA TRIO: A multinational, multicenter, phase II study of tesetaxel plus 3 different PD-(L)1 inhibitors in patients with metastatic triple negative breast cancer (TNBC) and tesetaxel monotherapy in elderly patients with her2- metastatic breast cancer (MBC)

Background Chemotherapy (CT) treatments with robust efficacy that preserve quality of life are needed. Tesetaxel (T) 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; and preclinical evidence of central nervous system (CNS) penetration and improved activity against CT-resistant tumors. More than 600 pts have been treated with T in clinical studies. T had robust monotherapy activity in a phase 2 study in 38 pts with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45%. Trial design CONTESSA TRIO is a 2-cohort, multinational, multicenter, Phase 2 study. In Cohort 1, 90 pts (with potential expansion to up to 150 pts) with metastatic TNBC who have not received prior CT for advanced disease will be randomized 1:1:1 to receive T at 27 mg/m2 Q3W plus either: (1) nivolumab at 360 mg Q3W; (2) pembrolizumab at 200 mg Q3W; or (3) atezolizumab at 1,200 mg Q3W. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the U.S. for the treatment of metastatic TNBC. The dual primary endpoints for Cohort 1 are ORR and progression-free survival (PFS). Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the 3 PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the 3 approved PD-L1 diagnostic assays. CONTESSA TRIO is the first randomized clinical study to compare 3 approved PD-(L)1 inhibitors. In Cohort 2, 40 elderly pts (with potential expansion to up to 60 pts) with HER2- MBC who have not received prior CT for advanced disease will receive T monotherapy at 27 mg/m2 Q3W. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS. Pts with CNS metastases are eligible for both cohorts. The Study was initiated in March 2019. Clinical trial identification EudraCT: 2018-004715-41. Legal entity responsible for the study Odonate Therapeutics, Inc. Funding Odonate Therapeutics, Inc. Disclosure S.M. Tolaney: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Cyclacel; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Odonate Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Nektar Therapeutics; Advisory / Consultancy: Tesaro; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy: Puma Biotechnology. J.L. Blum: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Medivation; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Bristol-Myers Squibb. A. Chan: Research grant / Funding (institution): Eisai; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Prime Oncology; Travel / Accommodation / Expenses: Pierre Fabre. Y. Feng: Research grant / Funding (institution), Full / Part-time employment: Chi Mei Medical Center. S. Kim: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sanofi-Genzyme; Research grant / Funding (institution): DongKook Pharmaceutical. M. Liu: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca. M. Oliveira: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Philips Healthcare; Research grant / Funding (institution): Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Boehringer-Ingelheim; Travel / Accommodation / Expenses: Pierre-Fabre; Travel / Accommodation / Expenses: GP Pharma; Travel / Accommodation / Expenses: Grunenthal. M. Pavic: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Astellas Pharma; Travel / Accommodation / Expenses: Taiho Pharmaceutical; Travel / Accommodation / Expenses: Bayer. H.S. Rugo: Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Roche/Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Pfizer; Travel / Accommodation / Expenses: Puma Biotechnology; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: MacroGenics; Honoraria (self): Celltrion; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution), Mandatory publication support: Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Odonate Therapeutics; Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Roche/Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Pfizer; Travel / Accommodation / Expenses: Puma Biotechnology; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: MacroGenics; Honoraria (self): Celltrion; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution), Mandatory publication support: Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Odonate Therapeutics. L. Schwartzberg: Advisory / Consultancy, Research grant / Funding (institution): Helsinn; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: Heron Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony: Coherus BioSciences; Speaker Bureau / Expert testimony: Puma Biotechnology. A. Stradella: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Celgene. S. Kroll: Shareholder / Stockholder / Stock options, Full / Part-time employment: Odonate Therapeutics. J. O’Connell: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Odonate Therapeutics; Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: inVentiv Health. T. Wei: Shareholder / Stockholder / Stock options, Full / Part-time employment: Odonate Therapeutics. E.A. Mittendorf: Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Merck; Advisory / Consultancy: Peregrine Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Sellas Lifesciences; Advisory / Consultancy: Tapimmune. All other authors have declared no conflicts of interest.