Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab – study protocol
J. C. Janssen,
B. van Dijk,
K. de Joode,
M. J. B. Aarts,
F. W. P. J. van den Berkmortel,
C. U. Blank,
M. J. Boers-Sonderen,
A. J. M. van den Eertwegh,
J. W. B. de Groot,
M. Jalving,
M. J. A. de Jonge,
A. Joosse,
E. Kapiteijn,
A. M. Kamphuis-Huismans,
K. A. T. Naipal,
D. Piersma,
B. Rikhof,
H. M. Westgeest,
G. Vreugdenhil,
E. Oomen-de Hoop,
E. E. A. P. Mulder,
Astrid A. M. van der Veldt
Affiliations
J. C. Janssen
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
B. van Dijk
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
K. de Joode
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
M. J. B. Aarts
Department of Medical Oncology, Maastricht UMC+
F. W. P. J. van den Berkmortel
Department of Medical Oncology, Zuyderland MC
C. U. Blank
Department of Medical Oncology, NKI-AvL
M. J. Boers-Sonderen
Department of Medical Oncology, Radboudumc
A. J. M. van den Eertwegh
Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam
J. W. B. de Groot
Department of Medical Oncology, Isala Zwolle
M. Jalving
Department of Medical Oncology, UMC Groningen
M. J. A. de Jonge
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
A. Joosse
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
E. Kapiteijn
Department of Medical Oncology, Leiden UMC
A. M. Kamphuis-Huismans
Department of Medical Oncology, UMC Utrecht
K. A. T. Naipal
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
D. Piersma
Department of Medical Oncology, Medisch Spectrum Twente
B. Rikhof
Department of Medical Oncology, Medisch Centrum Leeuwarden
H. M. Westgeest
Department of Medical Oncology, Amphia Ziekenhuis
G. Vreugdenhil
Department of Medical Oncology, Maxima Medisch Centrum Veldhoven
E. Oomen-de Hoop
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
E. E. A. P. Mulder
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
Astrid A. M. van der Veldt
Department of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute
Abstract Background Patients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with a combination of immune checkpoint inhibitors (ICIs), consisting of ipilimumab and nivolumab. This combination therapy is associated with severe immune related adverse events (irAEs) in about 60% of patients. In current clinical practice, patients are usually treated with ICIs for up to two years or until disease progression or the occurrence of unacceptable AEs. The incidence of irAEs gradually increases with duration of treatment. While durable tumour responses have been observed after early discontinuation of treatment, no consensus has been reached on optimal treatment duration. The objective of the Safe Stop IPI-NIVO trial is to evaluate whether early discontinuation of ICIs is safe in patients with irresectable stage III or metastatic melanoma who are treated with combination therapy. Methods The Safe Stop IPI-NIVO trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 80 patients with irresectable stage III or metastatic melanoma who are treated with combination therapy of ipilimumab-nivolumab and have a complete or partial response (CR/PR) according to RECIST v1.1 will be included to early discontinue maintenance therapy with anti-PD-1. The primary endpoint is the rate of ongoing response at 12 months after start of ICI. Secondary endpoints include ongoing response at 24 months, disease control at different time points, melanoma specific and overall survival, the incidence of irAEs and health-related quality of life. Discussion From a medical, healthcare and economic perspective, overtreatment should be prevented and shorter treatment duration of ICIs is preferred. If early discontinuation of ICIs is safe for patients who are treated with the combination of ipilimumab-nivolumab, the treatment duration of nivolumab could be shortened in patients with a favourable tumour response. Trial registration ClinicalTrials.gov ID NCT05652673, registration date: 08–12-2022.
