L3 Update of the OpACIN and OpACIN-neo trials: 36-months and 24-months relapse-free survival after (neo)adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma patients

Background Before adjuvant checkpoint inhibition the 5-year overall survival (OS) rate was poor ( Materials and Methods The phase 1b OpACIN trial included 20 stage IIIB/IIIC melanoma patients, which were randomized to receive IPI 3 mg/kg plus NIVO 1 mg/kg either adjuvant 4 cycles or split 2 cycles neoadjuvant and 2 adjuvant. In the phase 2 OpACIN-neo trial, 86 patients were randomized to 2 cycles neoadjuvant treatment, either in arm A: 2x IPI 3 mg/kg plus NIVO 1 mg/kg q3w (n=30), arm B: 2x IPI 1 mg/kg plus NIVO 3 mg/kg q3w (n=30), or arm C: 2x IPI 3 mg/kg q3w followed immediately by 2x NIVO 3 mg/kg q3w (n=26). Pathologic response was defined as Results Only 1 of 71 (1.4%) patients with a pathologic response on neoadjuvant therapy had relapsed, versus 16 of 23 patients (69.6%) without a pathologic response, after a median follow-up of 36 months for the OpACIN and 24 months for the OpACIN-neo trial. In the OpACIN trial, the estimated 3-year RFS rate for the neoadjuvant arm was 80% (95% CI: 59%-100%) versus 60% (95% CI: 36%-100%) for the adjuvant arm. Median RFS was not reached for any of the arms within the OpACIN-neo trial. Estimated 24-months RFS rate was 84% for all patients (95% CI: 76%-92%); 90% for arm A (95% CI: 80%-100%), 78% for arm B (95% CI: 63%-96%) and 83% for arm C (95% CI: 70%-100%). Baseline interferon-γ gene expression score and tumor mutational burden predict response. Conclusions OpACIN for the first time showed a potential benefit of neoadjuvant IPI plus NIVO versus adjuvant immunotherapy, whereas the OpACIN-neo trial confirmed the high pathologic response rates that can be achieved by neoadjuvant IPI plus NIVO. Both trials show that pathologic response can function as a surrogate markers for RFS. Clinical trial information NCT02437279, NCT02977052 Disclosure Information J.M. Versluis: None. E.A. Rozeman: None. A.M. Menzies: F. Consultant/Advisory Board; Modest; BMS, MSD, Novartis, Roche, Pierre-Fabre. I.L.M. Reijers: None. O. Krijgsman: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; BMS. E.P. Hoefsmit: None. B.A. van de Wiel: None. K. Sikorska: None. C. Bierman: None. P. Dimitriadis: None. M. Gonzalez: None. A. Broeks: None. R.M. Kerkhoven: None. A.J. Spillane: None. J.B.A.G. Haanen: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; BMS, MSD, Neon Therapeutics, Novartis. F. Consultant/Advisory Board; Modest; BMS, MSD, Novartis, Pfizer, AZ/MedImmune, Rocher/Genentech, Ipsen, Bayer, Immunocore, SeattleGenetics, Neon Therapeutics, Celsius Therapeutics, Gadet, GSK. W.J. van Houdt: None. R.P.M. Saw: None. H. Eriksson: None. A.C.J. van Akkooi: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; Amgen, BMS, Novartis. F. Consultant/Advisory Board; Modest; Amgen, BMS, Novartis, MSD Merck, Merck-Pfizer, 4SC. R.A. Scolyer: F. Consultant/Advisory Board; Modest; MSD, Neracare, Myriad, Novartis. T.N. Schumacher: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; MSD, BMS, Merck. E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; AIMM Therapeutics, Allogene Therapeutics, Amgen, Merus, Neogene Therapeutics, Neon Therapeutics. F. Consultant/Advisory Board; Modest; Adaptive Biotechnologies, AIMM Therapeutics, Allogene Therapeutics, Amgen, Merus, Neon Therapeutics, Scenic Biotech. Other; Modest; Third Rock Ventures. G.V. Long: F. Consultant/Advisory Board; Modest; Aduro, Amgen, BMS, Mass-Array, Pierre-Fabre, Novartis, Merck MSD, Roche. C.U. Blank: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; BMS, Novartis, NanoString. E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Uniti Cars, Neon Therapeutics, Forty Seven. F. Consultant/Advisory Board; Modest; BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre-Fabre.