The effect of a single dose of nivolumab prior to isolated limb perfusion for patients with in-transit melanoma metastases: An interim analysis of a phase Ib/II randomized double-blind placebo-controlled trial (NivoILP trial)
Carl-Jacob Holmberg, Lisanne P Zijlker, Dimitrios Katsarelias, Anne E Huibers, Michel W J M Wouters, Yvonne Schrage, Sophie J M Reijers, Johannes V van Thienen, Dirk J Grünhagen, Anna Martner, Jonas A Nilsson, Alexander C J van Akkooi, Lars Ny, Winan J van Houdt, Roger Olofsson Bagge, Carl-Jacob Holmberg, Lisanne P Zijlker, Dimitrios Katsarelias, Anne E Huibers, Michel W J M Wouters, Yvonne Schrage, Sophie J M Reijers, Johannes V van Thienen, Dirk J Grünhagen, Anna Martner, Jonas A Nilsson, Alexander C J van Akkooi, Lars Ny, Winan J van Houdt, Roger Olofsson Bagge
Abstract
Objective: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM).
Methods: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP. The primary endpoint was complete response (CR) rate at three months, and safety in terms of incidence and severity of adverse events (AEs).
Results: A total of 20 patients were included. AEs of any grade occurred in 90% of patients in the nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 3 AEs were reported in 40% and 30% respectively, most commonly related to wound infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in the placebo arm. The 1-year OS was 100% in both arms.
Conclusion: For patients with melanoma ITM, the addition of a single systemic dose of nivolumab the day before ILP is considered safe and feasible with promising efficacy. Accrual will continue in a phase 2 trial.
Keywords: Anti-PD1; In-transit metastases; Isolated limb perfusion; Melanoma.
Conflict of interest statement
Declaration of competing interest ACJvA is a member of the Advisory Board for, and received consultancy honoraria from, Amgen, Bristol-Myers Squibb, Neracare, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC. WvH has received institutional honoraria, speakers honorarium, or institutional research grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Belpharma, Sanofi and Sirius Medical. ROB has received institutional research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme. Remaining authors have no conflicts of interest to declare.
© 2024 Published by Elsevier Ltd.
Source: PubMed