1140TiP - 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

Background

Patients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with combination therapy of the immune checkpoint inhibitors (ICIs) 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 with a tumor response are usually treated with ICIs for years, while durable tumor responses have been observed after early discontinuation of treatment. To improve quality of life for patients, a shorter treatment duration of ICIs is preferred. 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.

Trial design

The Safe Stop IPI-NIVO trial is a nationwide, multicenter, prospective, single-arm, interventional study in the Netherlands (NCT05652673). 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. After inclusion in the trial, follow up will be conducted for five years and will include laboratory measurements, imaging for response evaluation and questionnaires on the health-related quality of life (HRQoL). These HRQoL questionnaires consist of the EuroQoL EQ-5D-5L, the FACT-Melanoma, the Cancer Worry Scale and the Institute for Medical Technology Assessment resource use questionnaires. In May 2024, the study was open for inclusion in 12 Dutch melanoma centers and 21 patients were included.

Clinical trial identification

NCT05652673.

Editorial acknowledgement

Legal entity responsible for the study

Erasmus Medical Center.

Funding

Transformatiedeal of the Dutch Federation of University Medical Centres.

Disclosure

K. de Joode: Non-Financial Interests, Institutional, Other, received travel expenses from Ipsen, outside the submitted work: Ipsen. F. Van Den Eertwegh: Non-Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Research Grant: Sanofi, Bristol Myers Squibb, TEVA, Idera. M. Jalving: Non-Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Pierre Fabre, AstraZeneca. E. Kapiteijn: Non-Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Pierre Fabre, Novartis, Immunocore, Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Delcath, Novartis, Pierre Fabre. D. Piersma: Non-Financial Interests, Institutional, Advisory Board: Novartis, Pierre Fabre, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis. H.M. Westgeest: Financial Interests, Institutional, Advisory Board: Merck. A.A.M. Van der Veldt: Financial Interests, Institutional, Advisory Board: BMS, Eisai, Ipsen, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi. All other authors have declared no conflicts of interest.