Abstract 199TiP
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 (Other Study ID Numbers: XL184-312).
Legal entity responsible for the study
Exelixis.
Funding
Exelixis.
Disclosure
T. Yau: Advisory / Consultancy: Exelixis; Honoraria (self): Ipsen, Exelixis. L. Rimassa: Advisory / Consultancy: Lilly, Bayer, Baxter, Sirtex Medical, Italfarmaco, Sanofi, ArQule, Baxter, Ipsen, Exelixis, Amgen, Celgene, Eisai, Hengrui, MSD; Honoraria (self): AstraZeneca, AbbVie, Gilead, Roche; Travel / Accommodation / Expenses: ArQule, Ipsen. A-L. Cheng: Advisory / Consultancy, Advisory Board: Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix Ltd., Roche/Genentech, and IQVIA; Advisory / Consultancy, Consultancy: Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix Ltd., Roche/Genentech, and IQVIA; Honoraria (self): Bayer, Eisai, and Merck Sharp Dohme, Merck Serono, Novartis, Ono Pharmaceutical, Roche/Genentech, and IQVIA. J-W. Park: Advisory / Consultancy, Advisory board: Astra-Zeneca, Ono, BMS, Bayer, Midatech; Research grant / Funding (self): Ono-BMS, AstraZeneca, Blueprint, Roche, Eisai, Exelixis, Kowa; Advisory / Consultancy, Consultancy: Ono, Genetech, Roche, BMS, Bayer, Ipsen; Honoraria (self): Bayer, Ono, Eisai. F. Braiteh: Shareholder / Stockholder / Stock options: Agios; Bristol-Myers Squibb; Clovis Oncology; Insys Therapeutics; Tesaro; Honoraria (self): Abbott Nutrition; Amgen; ARIAD; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Genentech/Roche; HERON; Incyte; Insys Therapeutics; Insys Therapeutics; Ipsen; Lexicon; Lilly; Taiho Pharmaceutical; Advisory / Consultancy: Ambry Genetics; Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Clovis Oncology; Genentech/Roche; Incyte; Insys Therapeutics; Ipsen; Ipsen; Lexicon; Lilly; Merck; Merrimack; Pfizer; Regeneron; Sanofi; Speaker Bureau / Expert testimony: Amgen; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Genentech/Roche; Incyte; Insys Therapeutics; Ipsen; Lilly; Merck; Merck; Merrimack; Pfizer; Taiho Pharmaceutical; Travel / Accommodation / Expenses: - Amgen; AstraZeneca/MedImmune; Bayer; Bayer/Onyx; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Clovis Oncology; Exelixis; HERON; Incyte; Insys Therapeutics; Ipsen; Lexicon; Merrimack; Novartis; Pfizer; Regeneron; Roche/Genentech; Sanofi; Taiho Ph. F. Benzaghou: Full / Part-time employment: IPSEN; Shareholder / Stockholder / Stock options: IPSEN. P. Thuluvath: Honoraria (self): AbbVie; Gilead Sciences; Advisory / Consultancy: AbbVie; Eisai; Gilead Sciences; Speaker Bureau / Expert testimony: AbbVie; Gilead Sciences; Research grant / Funding (institution): AbbVie (Inst); Allergan (Inst); Conatus (Inst); Cymabay Therapeutics (Inst); Eisai (Inst); Sillajen (Inst); Target Pharmasolutions (Inst); Tobira Therapeutics (Inst); Zydus Pharmaceuticals (Inst). S. Hazra: Full / Part-time employment: Exelixis; Shareholder / Stockholder / Stock options: Exelixis. S. Milwee: Full / Part-time employment: Exelixis; Shareholder / Stockholder / Stock options: Exelixis. B. Tan: Research grant / Funding (institution): Exelixis. A.X. Zhu: Advisory / Consultancy: AstraZeneca; Bayer; Bristol-Myers Squibb; eisai; Exelixis; Lilly; Merck; Novartis; Sanofi; Research grant / Funding (institution): Bayer (Inst); Bristol-Myers Squibb (Inst); Lilly (Inst); Merck (Inst); Novartis (Inst). R.K. Kelley: Advisory / Consultancy, funding to institution: Agios, AstraZeneca, Bayer, BMS ; Advisory / Consultancy, funding to self: IDMC: Genentech/Roche ; Research grant / Funding (institution): Agios, AstraZeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Medimmune, Merck, Novartis, QED, Taiho. All other authors have declared no conflicts of interest.
Resources from the same session
314P - An EGF motif of Del1 inhibits efficient angiogenesis and suppresses tumour growth in vivo
Presenter: Hisataka Kitano
Session: Poster display session
Resources:
Abstract
315P - Inhibition of JAK1 sensitizes human head and neck cancer cells to cetuximab
Presenter: James Bonner
Session: Poster display session
Resources:
Abstract
316TiP - Neoadjuvant and adjuvant pembrolizumab (pembro) plus standard of care (SOC) in patients (pts) with resectable locally advanced (LA) head and neck squamous cell carcinoma (HNSCC): The phase III KEYNOTE-689 study
Presenter: Ezra Cohen
Session: Poster display session
Resources:
Abstract
322P - Three-year overall survival update from the PACIFIC trial
Presenter: Yi-Long Wu
Session: Poster display session
Resources:
Abstract
323P - Novel tumour mutation score versus tumour mutation burden in predicting survival after immunotherapy in pan-cancer from MSK-IMPACT cohort
Presenter: Yuan Li
Session: Poster display session
Resources:
Abstract
324P - A novel anti-PD-1 antibody HLX10 study led to the initiation of combination immunotherapy
Presenter: Tsu Yi Chao
Session: Poster display session
Resources:
Abstract
325P - Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma
Presenter: Lawrence Wong
Session: Poster display session
Resources:
Abstract
326P - Autologous V gamma 9 V delta 2 T cell therapy to target Epstein Barr Virus (EBV)-related malignancies
Presenter: Esdy Rozali
Session: Poster display session
Resources:
Abstract
327P - Neoantigen profile of hepatocellular carcinoma reveals its correlation with tumour progression and clonal evolution
Presenter: Xiaolong Liu
Session: Poster display session
Resources:
Abstract
328P - A retrospective analysis of patients with non-small cell lung cancer who developed drug-induced lung disorder by immune checkpoint inhibitors
Presenter: Fumiko Hayashi
Session: Poster display session
Resources:
Abstract