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01-12-2021 | Liver Resection | Study protocol

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

Authors: David J. Pinato, Alessio Cortellini, Ajithkumar Sukumaran, Tom Cole, Madhava Pai, Nagy Habib, Duncan Spalding, Mikael H. Sodergren, Maria Martinez, Tony Dhillon, Paul Tait, Robert Thomas, Caroline Ward, Hemant Kocher, Vincent Yip, Sarah Slater, Rohini Sharma

Published in: BMC Cancer | Issue 1/2021

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.

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Title: PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma
Authors: David J. Pinato
Alessio Cortellini
Ajithkumar Sukumaran
Tom Cole
Madhava Pai
Nagy Habib
Duncan Spalding
Mikael H. Sodergren
Maria Martinez
Tony Dhillon
Paul Tait
Robert Thomas
Caroline Ward
Hemant Kocher
Vincent Yip
Sarah Slater
Rohini Sharma
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Liver Resection
Liver Resection
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08033-x

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