Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy

Date

29 Sep 2019

Session

Poster Display session 2

Presenters

Lorenza Rimassa

Citation

Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247

Authors

L. Rimassa1, A. Cheng2, F. Braiteh3, A. Chaudhry4, F. Benzaghou5, P. Thuluvath6, S. Hazra7, A.E. Borgman-Hagey8, B. Tan9, Z.K. Kayali10, A.X. Zhu11, R.K. Kelley12

Author affiliations

  • 1 Humanitas Clinical And Research Center, Irccs, Humanitas Cancer Center, 20089 - Rozzano/IT
  • 2 College Of Medicine, National Taiwan University Hospital, 100 - New Taipei city/TW
  • 3 Oncology, Comprehensive Cancer Centers of Nevada, 89169 - Las Vegas/US
  • 4 Medical Oncology, Summit Cancer Centers, Spokane/US
  • 5 Clinical Development, Ipsen Innovation, Les Ulis/FR
  • 6 The Institute For Digestive Health & Liver Disease, Mercy Medical Center, Baltimore/US
  • 7 Clinical Science, Exelixis, Alameda/US
  • 8 Clinical Research, Exelixis, Alameda/US
  • 9 Oncology, Siteman Cancer Center, St. Louis/US
  • 10 Gastroenterology, Riverside Community Hospital, Rialto/US
  • 11 Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, 02114 - Boston/US
  • 12 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94158 - San Francisco/US
More

Resources

Abstract 4710

Background

C inhibits tyrosine kinases involved in tumor growth, angiogenesis, and immune regulation, including MET, VEGFR, and TAM kinases (Tyro3, AXL, MER). C is approved in the United States and Europe for treatment of aHCC after prior S based on improved overall survival (OS) vs placebo in the phase 3 CELESTIAL trial (Abou-Alfa NEJM 2018). C may promote an immune-permissive tumor environment, which could enhance response to immune checkpoint inhibitors. C is being evaluated in combination with the anti-PD-L1 antibody A in multiple tumor types including HCC in a phase 1 study; recommended dose, preliminary clinical activity, and safety of the combination have been established in aRCC (Agarwal Ann Oncol 2018). A in combination with bevacizumab, an anti-VEGF antibody, has shown preliminary clinical activity in first-line aHCC (Pishvaian Ann Oncol 2018). Here, we present the study design of a phase 3 trial of C + A vs S in pts with aHCC who have not received prior systemic therapy.

Trial design

This global, randomized, open-label phase 3 trial (NCT03755791) is evaluating the efficacy and safety of C + A vs S as first-line treatment for aHCC. C vs S will also be evaluated as a secondary endpoint. Eligibility criteria include age ≥18 years, BCLC stage B or C, Child-Pugh A, ECOG PS ≤ 1, and measurable disease per RECIST 1.1. Pts are randomized 2:1:1 to an experimental arm of C (40 mg qd) + A (1200 mg infusion q3w), a control arm of S (400 mg bid), and a C monotherapy arm (60 mg qd). 740 pts are planned to be enrolled at ∼250 sites globally. Randomization is stratified by disease etiology (HBV [with or without HCV], HCV [without HBV], or other), region (Asia, other), and the presence of extrahepatic disease and/or macrovascular invasion (yes, no). OS and progression-free survival (PFS) for C+A vs S are primary endpoints, and PFS for C vs S is a secondary endpoint. Additional endpoints include safety, pharmacokinetics, and correlation of biomarker analyses with clinical outcomes. The first patient was enrolled in December 2018, and enrollment is ongoing.

Clinical trial identification

NCT03755791.

Editorial acknowledgement

Julie Lougheed, Exelixis Inc.

Legal entity responsible for the study

Exelixis Inc.

Funding

Exelixis Inc.

Disclosure

L. Rimassa: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Gilead; Honoraria (self), Honoraria paid for lectures: Roche; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Bayer; Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy: Italfarmaco; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): ArQule; Advisory / Consultancy: Baxter; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Agios. A. Cheng: Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self): Merck Sharp Dohme; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin, Ltd; Speaker Bureau / Expert testimony: Amgen Taiwan. F. Braiteh: Shareholder / Stockholder / Stock options: Agios; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Clovis Oncology; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Insys Therapeutics; Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Tesaro; Honoraria (self): Abbott Nutrition; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self): ARIAD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech/Roche; Honoraria (self), Travel / Accommodation / Expenses: HERON; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Insys Therapeutics; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lexicon; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Taiho Pharmaceutical; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merrimack; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Regeneron; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca/MedImmune; Travel / Accommodation / Expenses: Bayer/Onyx; Travel / Accommodation / Expenses: Novartis. F. Benzaghou: Shareholder / Stockholder / Stock options, Full / Part-time employment: Ipsen Pharma. P. Thuluvath: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AbbVie; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Gilead Sciences; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Allergan; Research grant / Funding (institution): Conatus; Research grant / Funding (institution): Cymabay Therapeutics; Research grant / Funding (institution): Sillajen; Research grant / Funding (institution): Target Pharmasolutions; Research grant / Funding (institution): Tobira Therapeutics; Research grant / Funding (institution): Zydus Pharmaceuticals. S. Hazra: Shareholder / Stockholder / Stock options, Full / Part-time employment: Exelixis Inc. A.E. Borgman-Hagey: Shareholder / Stockholder / Stock options, Full / Part-time employment: Exelixis Inc. B. Tan: Research grant / Funding (institution): Exelixis. A.X. Zhu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Exelixis; Research grant / Funding (institution): Bayer. R.K. Kelley: Advisory / Consultancy, Research grant / Funding (institution): Agios; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution), Advisory fees to Institution: BMS; Advisory / Consultancy, IDMC funding: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Unfunded Advisory/Steering Committee: Exelixis; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): QED; Research grant / Funding (institution): Taiho. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings