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.
Resources from the same session
2674 - Multicenter Phase I Trial of Trastuzumab Emtansine (T-DM1) in Combination with Non-Pegylated Liposomal Doxorubicin (NPLD) in HER2[+] Metastatic Breast Cancer (MBC). THELMA Study
Presenter: Elena López-Miranda
Session: Poster Display session 2
Resources:
Abstract
1398 - Phase 1 study of liposomal formulation of eribulin (E7389-LF) in patients (pts) with advanced solid tumors: primary results of dose-escalation part
Presenter: Noboru Yamamoto
Session: Poster Display session 2
Resources:
Abstract
5818 - Polo-like Kinase 1 inhibitor onvansertib synergizes with paclitaxel in breast cancer carrying p53 mutation
Presenter: Antonio Giordano
Session: Poster Display session 2
Resources:
Abstract
5927 - Phase 1b study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple negative breast cancer (NCT02474173).
Presenter: Robert Wesolowski
Session: Poster Display session 2
Resources:
Abstract
1695 - Impact of pertuzumab and T-DM1 on prognosis of HER2-positive metastatic breast cancer (MBC) and factors affecting their efficacy: results from the AGMT_MBC-Registry
Presenter: Simon Peter Gampenrieder
Session: Poster Display session 2
Resources:
Abstract
1742 - Clinical profile and outcome of HER2 positive breast cancer patients with brain metastases treated with HER2 targeted therapy: Real world experience.
Presenter: Prabhat Bhargava
Session: Poster Display session 2
Resources:
Abstract
1846 - Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer: results of single arm phase IV COMACHI study
Presenter: Norikazu Masuda
Session: Poster Display session 2
Resources:
Abstract
5385 - Anti HER-2 Therapies and Left Ventricular Dysfunction The Renaissance Study
Presenter: ANDRES DANIELE
Session: Poster Display session 2
Resources:
Abstract
3320 - Safety and efficacy of T-DM1 in 128 patients with advanced HER2+ breast cancer: The Royal Marsden experience.
Presenter: Nicolò Battisti
Session: Poster Display session 2
Resources:
Abstract
4540 - Use of trastuzumab emtansine (T-DM1; K) after pertuzumab + trastuzumab (PH) in patients with HER2-positive metastatic breast cancer (mBC): challenges in assessing effectiveness of treatment sequencing in the real world (RW)
Presenter: Thibaut Sanglier
Session: Poster Display session 2
Resources:
Abstract