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.
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.
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 [
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 (OpACIN-neo 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.
Clinical trial identification
Legal entity responsible for the study
P. Kvistborg: Advisory board: Neon therapeutics, Merck, Personalis. J.V. Thienen: Advisory board: MSD, Bristol-Myers Squibb. B. Stegenga, B. Lamon: Employee of Bristol-Myers Squibb. J.B. Haanen: Advisory role: Bristol-Myers Squibb, MSD, Pfizer, Roche, Novartis, Neon Therapeutics Research grants: Bristol-Myers Squibb, MSD, GSK. C.U. Blank: Advisory role: Bristol-Myers Squibb, MSD, GSK, Roche, Novartis, Lilly, Pfizer Research grants: Bristol-Myers Squibb, Novartis. All other authors have declared no conflicts of interest.