Abstract 575TiP
Background
Antiangiogenic agents have demonstrated antitumor properties in endocrine malignancies regardless of their primary origin. Experience with immune-checkpoint inhibitors is limited in this area and early results when used as single agents are discouraging. The aim of this trial is to assess the efficacy and safety of the combination of cabozantinib and atezolizumab, which may overcome the resistance in previously treated metastatic endocrine tumors.
Trial design
CABATEN is a prospective, multi-center, open-label, phase II study of cabozantinib plus atezolizumab in advanced and refractory tumours of the endocrine system stratified into 6 cohorts: (1) well differentiated neuroendocrine tumors (NETs) of the lung, (2) anaplastic thyroid cancer, (3) adrenocortical carcinoma, (4) pheochromocytoma/ paraganglioma, (5) well differentiated gastroenteropancreatic NETs, (6) grade 3 neuroendocrine neoplasms. Patients (pts) included in the trial must have progressed on standard therapies in each setting, with no limit to the number of previous lines. For pts included in cohort 2, inclusion in the first-line is allowed if pts are not eligible for chemotherapy. All pts will receive atezolizumab 1200 mg every 3 weeks and cabozantinib 40 mg daily continuously until progression, unacceptable toxicity or consent withdrawal. Cabozantinib dose reduction to 20 mg daily is allowed. The primary endpoint is overall response rate (ORR) assessed by investigators according to RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, quality of life, safety and a wide panel of biomarkers in blood and tumor samples. Using a Simon II stage design with a null hypothesis of 5% ORR from previous studies and an alternate hypothesis of 20% ORR, 24 pts per cohort (9 in a first stage and 15 in a second stage) are needed. Accrual started in October 2020. To date, 55 out of 144 expected pts have been enrolled.
Clinical trial identification
EudraCT 2019-002279-32; NCT04400474.
Editorial acknowledgement
Legal entity responsible for the study
Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).
Funding
Ipsen and Roche.
Disclosure
E. Grande: Financial Interests, Personal, Invited Speaker: Adacap; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Caris Life Sciences; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Eusa Pharma; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck KGaA; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: ONCODNA (Biosequence); Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme; Non-Financial Interests, Institutional, Research Grant: Astellas; Non-Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Ipsen; Non-Financial Interests, Institutional, Research Grant: Lexicon; Non-Financial Interests, Institutional, Research Grant: MTEM/Threshold; Non-Financial Interests, Institutional, Research Grant: Nanostring; Non-Financial Interests, Institutional, Research Grant: ROCHE; Non-Financial Interests, Institutional, Research Grant: Pfizer. R. Garcia-Carbonero: Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: AAA; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Advanz Pharma; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Bayer; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: BMS; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: HMP; Financial Interests, Personal, Other, Scientific Advice, Speakers ureau, Honoraria: Ipsen; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Merk; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Midatech Pharma; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: MSD; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Novartis; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Pharmamar; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Pfizer; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Pierre Fabre; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Roche; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Sanofi; Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: Servier; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: BMS; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Institutional, Funding: Armo; Financial Interests, Institutional, Funding: Biosciences; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Pharmacyclics; Financial Interests, Institutional, Funding: Boston biomedicals; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Boehringer; Financial Interests, Institutional, Funding: Sysmex; Financial Interests, Institutional, Funding: Gilead Sciences; Financial Interests, Institutional, Funding: Servier; Financial Interests, Institutional, Funding: Adacap; Financial Interests, Institutional, Funding: VCN; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Pharmamar; Non-Financial Interests, Personal, Member, Member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), Member of the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS): GETNE; Non-Financial Interests, , Member: EORTC; Non-Financial Interests, , Member: ASCO; Non-Financial Interests, , Member: ESMO; Non-Financial Interests, , Member: SEOM; Non-Financial Interests, , Member: TTD; Non-Financial Interests, , Member: GEMCAD. A. Teule: Financial Interests, Personal, Other, Speaking, writing, public presentations, advisory service, travel grants: Novartis; Financial Interests, Personal, Other, Speaking, writing, public presentations, advisory service, travel grants: Ipsen; Financial Interests, Personal, Other, Speaking, writing, public presentations, advisory service, travel grants: AAA; Financial Interests, Personal, Other, Speaking, writing, public presentations, advisory service, travel grants: Pfizer; Financial Interests, Personal, Other, Speaking, Writing, Public Presentations, Advisory Service, Travel Grants: AstraZeneca. M. Benavent Viñuales: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Ipsen. P. Jimenez-Fonseca: Financial Interests, Personal, Advisory Board: Bristol; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Mylan; Financial Interests, Personal, Advisory Board: Baxter; Financial Interests, Personal, Invited Speaker: HRA Pharma; Financial Interests, Personal, Invited Speaker: LEOPharma; Financial Interests, Personal, Invited Speaker: Rovi; Financial Interests, Personal, Invited Speaker: Sanofi. J. Molina-Cerrillo: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Research Grant: Pfizer. C. López: Financial Interests, Personal, Other, Honoraria you have directly received for any speaker, consultancy or advisory role or similar: Ipsen; Financial Interests, Personal, Other, Honoraria you have directly received for any speaker, consultancy or advisory role or similar: Roche; Financial Interests, Personal, Other, Honoraria you have directly received for any speaker, consultancy or advisory role or similar: Eisai; Financial Interests, Personal, Other, Honoraria you have directly received for any speaker, consultancy or advisory role or similar: Novartis; Financial Interests, Personal, Other, Honoraria you have directly received for any speaker, consultancy or advisory role or similar: Pfizer; Financial Interests, Personal, Other, Honoraria you have directly received for any speaker, consultancy or advisory role or similar: AAA; Financial Interests, Personal, Principal Investigator: Ipsen; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Novartis. M. Llanos: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Other, Speaker & advisory: Amgen; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: AAA; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Other, Speaker & advisory: Roche; Financial Interests, Personal, Invited Speaker: Merk; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Bristol; Financial Interests, Personal, Invited Speaker: Sanofi. I. Sevilla: Financial Interests, Personal, Other, Speaker and Advisory: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Syrtex; Financial Interests, Personal, Invited Speaker: Pharmamar; Financial Interests, Personal, Advisory Role: AMGEN; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: AAA. J. Hernando: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: IPSEN; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AAA; Financial Interests, Personal, Invited Speaker: Angelini. F. Lista: Financial Interests, Personal, Other, Speaker and consultancy: BMS; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Gsk; Financial Interests, Personal, Invited Speaker: Janssen. B. Antón Pascual: Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Fresenius; Financial Interests, Personal, Invited Speaker: Angelini. J. Capdevila: Other, Speaker’s Bureau: Amgen; Other, Speaker’s Bureau: Bayer; Other, Speaker’s Bureau: Eisai; Other, Speaker’s Bureau: AAA; Other, Speaker’s Bureau: Ipsen; Other, Speaker’s Bureau: Pfizer; Other, Speaker’s Bureau: Merk; Other, Speaker’s Bureau: Sanofi; Other, Speaker’s Bureau: Novartis; Other, Speaker’s Bureau: Lilly; Other, Speaker’s Bureau: ITM; Other, Speaker’s Bureau: Hudchinson Pharma; Other, Speaker’s Bureau: Exelixis; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AAA; Financial Interests, Personal and Institutional, Research Grant: Ipsen; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Novartis; Other, Personal, Member, Chair of the Spanish Task Force for Neuroendocrine and Endocrine Tumor Group (GETNE) and Advisory member of the European Neuroendocrine Tumor Society (ENETS): GETNE. All other authors have declared no conflicts of interest.