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PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma

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Title: PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma
Authors: Pinato, D
Cortellini, A
Sukumaran, A
Cole, T
Pai, M
Habib, N
Spalding, D
Sodergren, M
Martinez, M
Dhillon, T
Tait, P
Thomas, R
Ward, C
Kocher, H
Yip, V
Slater, S
Sharma, R
Item Type: Journal Article
Abstract: Background After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. Methods The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. Discussion The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. Trial registration EudraCT Number: 2018–000987-27 Clinical trial registry & ID: ClinicalTrials.gov: NCT03682276.
Issue Date: 23-Mar-2021
Date of Acceptance: 12-Mar-2021
URI: http://hdl.handle.net/10044/1/88610
DOI: 10.1186/s12885-021-08033-x
ISSN: 1471-2407
Publisher: BioMed Central
Journal / Book Title: BMC Cancer
Volume: 21
Copyright Statement: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Sponsor/Funder: Wellcome Trust
Bristol Myers Squibb Pharmaceuticals Ltd (0034)
Funder's Grant Number: 204834/Z/16/Z
0081891031
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
HCC
Immunotherapy
PD-1
PD-L1
CTLA-4
CTLA-4
HCC
Immunotherapy
PD-1
PD-L1
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Hepatocellular
Hepatectomy
Humans
Immune Checkpoint Inhibitors
Ipilimumab
Liver Neoplasms
Neoadjuvant Therapy
Nivolumab
Outcome Assessment, Health Care
Humans
Carcinoma, Hepatocellular
Liver Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Neoadjuvant Therapy
Hepatectomy
Ipilimumab
Nivolumab
Outcome Assessment, Health Care
Immune Checkpoint Inhibitors
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1117 Public Health and Health Services
Publication Status: Published
Article Number: ARTN 301
Appears in Collections:Department of Surgery and Cancer
Institute of Global Health Innovation



This item is licensed under a Creative Commons License Creative Commons