Multicenter phase 2 study to identify the optimal neo-adjuvant combination scheme of ipilimumab (IPI) and nivolumab (NIVO) (OpACIN-neo)

TPS9606Background: The outcome of high risk stage III melanoma patients (pts) is poor, with a 5 year overall survival (OS) rate of < 50%. Adjuvant (adj) high dose IPI significantly improves 5 year progression free survival (PFS) and OS and adj NIVO improves the median PFS even more. In stage IV pts, the combination of IPI and NIVO improves response rates (RR) and PFS compared to monotherapy, but at cost of higher toxicity. Neo-adjuvant (neoadj) treatment may be a favorable approach as immune checkpoint inhibition (ICI) is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen. The phase Ib OpACIN study compared neoadj versus adj IPI plus NIVO. The pathological RR (pRR) was 80% in the neoadj arm, and to date after a median follow-up of 24 months, none of the responders has relapsed, while 4/10 pts have relapsed in the adj arm. Moreover, pts in the neoadj arm expanded more tumor-resident TCR clones than adj treated pts. Neoadj IPI+NIVO was feasible, but toxicity w...