A randomised phase III multicentre trial to evaluate the duration of anti-PD1 monoclonal antibody monotherapy in patients with metastatic melanoma (DANTE) – Stage 1 results


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Sarah Danson1,Ruth Plummer2,Christian Ottensmeier3,Jane Hook4,Helen Marshall5,Gurdeep Sagoo5,David Meads5,Janine Bestall5,Galina Velikova5,Ferdia Gallagher6,Alexandra Smith5,Sue Bell5,Ellen Mason5,Eszter Katona5,Simon Rodwell7,Pippa Corrie8
1University of Sheffield, Sheffield, UK,2Newcastle University, Newcastle, UK,3University of Southampton, Southampton, UK,4Leeds Teaching Hospitals NHS Trust, Leeds, UK,5University of Leeds, Leeds, UK,6University of Cambridge, Cambridge, UK,7Melanoma Focus, Cambridge, UK,8Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Abstract

Background

Immunotherapy has revolutionised the treatment of melanoma and other tumour types. In contrast to some immune checkpoint inhibitors which are given for a fixed duration of 12 weeks, the anti-PD1 antibodies pembrolizumab and nivolumab are licensed to be given every 2-6 weeks until disease progression, which can extend to several years. This is a significant burden to patients and the NHS. Many responses occur in the first year and can continue even after treatment is stopped. The optimal duration of treatment is a major research priority. We hypothesise that continuing treatment beyond 1 year is unnecessary, exposing patients to the risk of developing immune-related toxicities and incurring considerable costs.

Method

DANTE is a randomised multi-stage phase III non-inferiority trial. Patients receiving anti-PD1 monotherapy are registered into DANTE within 1 year of starting treatment. Those who remain progression-free at 1 year are then randomised to either a) stop treatment (with the option to restart anti-PD1 therapy or commence other treatment on progression) or b) continue until disease progression/unacceptable toxicity, or for a minimum of 2 years in the absence of progression/toxicity. Participants are followed up for 4 years. The primary outcome is progression-free survival. Secondary outcomes are quality of life, overall survival, response rate and duration, safety, cost effectiveness and patient acceptance of randomisation.

Results

The trial includes 3 interim stages to identify early lack of feasibility of recruitment or efficacy. The trial opened in September 2018 and aims to randomise 1208 participants. The results of the Stage 1 analysis of recruitment rate and patient acceptance of randomisation will be presented.

Conclusion

The outcomes of DANTE will be of national and international importance in melanoma and other cancers.