(Neo-)adjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage 3 melanoma – updated relapse free survival (RFS) data from the OpACIN trial and first biomarker analyses

Abstract

Background: The combination of IPI+NIVO induces high response rates and improved overall survival in late stage melanoma. T cell checkpoint inhibition is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen present, indicating that adjuvant immunotherapy will work most efficiently, when initiated prior to surgery. Methods: Two-arm Phase 1b feasibility trial consisting of 20 high risk AJCC stage 3B/C melanoma patients with palpable nodal disease receiving the combination of IPI 3mg/ kg and NIVO 1mg/kg, either adjuvant four courses after surgery, or split neo-adjuvant and adjuvant. Results: In this update 20 patients are evaluable. Neo-adjuvant application of IPI+NIVO was feasible and no surgery-associated adverse events were attributed to (neo-) adjuvant therapy. 18/20 patients had to stop earlier due to grade 3/4 toxicities. Neo-adjuvant IPI+NIVO reduced tumor load in 8/10 patients (3 pCR, 4 near pCRs [minimal remaining micro metastases], 1 pPR [<50% vital tumor cells], 1 pSD and 1 pPD). So far, none of the responders in the neo-adjuvant arm has relapsed. Relapse was observed for the 2 non-responders within the neo-adjuvant arm and for 3 patients within the adjuvant arm. We will present at ESMO 2017 the 18 months RFS update and in detail the biomarker analyses. Latter comprises RNA sequencing and NanostringTM microscope spatial profiling to identify biomarkers for response, and TCR sequencing, with the aim to distinguish T cell responses between both, the two treatment arms and between patients relapsing or remaining free of disease. Conclusions: The combination of IPI+NIVO in the (neo-)adjuvant treatment setting for high risk stage 3 melanoma patients is promising and currently tested in an international phase 2 randomized trial comparing different combination schemes (OpACINneo trial, NCT02977052) with the aim of preserving efficacy, but reducing toxicity. Biomarkers identifying patients responding upon neo-adjuvant IPI+NIVO and remaining relapse-free for a long time, will help to select the patients that need to be exposed to IPI+NIVO associated toxicity.