Abstract 4119
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.
Editorial acknowledgement
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: Grünenthal. 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.
Resources from the same session
5887 - Factors of importance in procuring tumoroids from colorectal liver metastasis biopsies for precision medicine.
Presenter: Lars Henrik Jensen
Session: Poster Display session 2
Resources:
Abstract
2196 - FUSAFE individual patient data meta-analysis (MA) to assess the performance of dihydropyrimidine dehydrogenase (DPD) gene polymorphisms for predicting grade 4-5 fluoropyrimidine (FP) toxicity
Presenter: Marie-Christine Etienne-Grimaldi
Session: Poster Display session 2
Resources:
Abstract
2859 - Treatments (tx) after progression to first-line FOLFOXIRI + bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and TRIBE-2 studies by GONO.
Presenter: Daniele Rossini
Session: Poster Display session 2
Resources:
Abstract
3888 - Randomized phase III study of sequential treatment with capecitabine or 5-fluorouracil (FP) plus bevacizumab (BEV) followed by the addition with oxaliplatin (OX) versus initial combination with OX+FP+ BEV in the first-line chemotherapy for metastatic colorectal cancer: The C-cubed study
Presenter: Takeshi Nagasaka
Session: Poster Display session 2
Resources:
Abstract
1065 - Early tumour shrinkage (ETS), depth of response (DpR) and associated survival outcomes in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) classified according to Köhne prognostic category: retrospective analysis of the panitumumab (Pmab) PRIME study
Presenter: Andrea Sartore-Bianchi
Session: Poster Display session 2
Resources:
Abstract
1702 - Randomized phase II trial of CAPOX with planned oxaliplatin stop-and-go strategy as adjuvant chemotherapy after curative resection of colon cancer (CCOG-1302 study)
Presenter: Hiroyuki Yokoyama
Session: Poster Display session 2
Resources:
Abstract
5104 - A metabolomic recurrence score for risk-stratification of elderly patients (pts) with early colorectal cancer (eCRC)
Presenter: Samantha Di Donato
Session: Poster Display session 2
Resources:
Abstract
5285 - RAS mutant allele fraction in plasma predicts benefit to anti-angiogenic based first line treatment in metastatic colorectal cancer
Presenter: Giulia Martini
Session: Poster Display session 2
Resources:
Abstract
1790 - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG
Presenter: Stephan Sahm
Session: Poster Display session 2
Resources:
Abstract
3059 - Intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): A randomized, multicenter, prospective, phase III trial
Presenter: Rongxin Zhang
Session: Poster Display session 2
Resources:
Abstract