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

doi:10.1016/j.ejso.2024.108265

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)

Eur J Surg Oncol. 2024 Mar 12;50(6):108265. doi: 10.1016/j.ejso.2024.108265. Online ahead of print.

Authors

Affiliations

¹ Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
² The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the Netherlands; Melanoma Institute Australia, Sydney, New South Wales, Australia.
³ Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the Netherlands.
⁵ The Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam, the Netherlands.
⁶ Erasmus Medical Center, Department of Surgical Oncology, Rotterdam, the Netherlands.
⁷ TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁸ Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Western Australia, Australia.
⁹ Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
¹⁰ Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹¹ Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: roger.olofsson.bagge@gu.se.

PMID: 38493679
DOI: 10.1016/j.ejso.2024.108265

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.