1739 - 18-months relapse-free survival (RFS) and biomarker analyses of OpACIN-neo: a study to identify the optimal dosing schedule of neoadjuvant (neoadj) Ipilimumab (IPI) + Nivolumab (NIVO) in stage III melanoma

Background

Primary analysis of the OpACIN-neo study testing 3 dosing schedules of neoadj IPI+NIVO identified 2 cycles IPI 1 mg/kg + NIVO 3 mg/kg (IPI1+NIVO3; arm B) as most favourable, with 20% grade 3-4 irAEs and a pathologic response rate (pRR) of 77%. After a median FU of 8.3 mo none of the pts with a pathologic response versus 9/21 (43%) of the non-responders had relapsed. Here we present updated RFS and biomarker analyses.

Methods

OpACIN-neo is a multicentre, randomized phase II trial in resectable stage III melanoma pts with ≥1 measurable lymph node metastasis (RECIST 1.1). 86 pts were randomized to arm A: 2x IPI3+NIVO1 Q3W (n = 30); B: 2x IPI1+NIVO3 Q3W (n = 30); or C: 2x IPI3 Q3W followed by 2x NIVO3 Q2W (n = 26). Lymph node dissection was planned at wk 6. Primary endpoints were toxicity, radiologic RR and pRR; RFS and biomarker analyses were secondary endpoints. Mutational profiles, gene expression signatures (GES) and immune protein expression were examined in baseline biopsies by whole exome seq, RNA seq and digital spatial profiling (DSP) analysis. Pre- and post-treatment plasma samples were profiled for 92 proteins.

Results

After a median FU of 17.7 mo, the median RFS was not reached in any of the arms. Estimated 18-mo RFS was 85% for all pts (95% CI 78%-93%), 90% for arm A (95% CI, 80%-100%), 82% for arm B (95% CI, 70%-98%) and 83% for arm C (95% CI, 70%-100%). Relapses were observed in 1/64 (2%) pathological responders versus 13/21 (62%) of the non-responders. High tumour mutational burden (TMB) and high interferon-y (IFN-y) signature were associated with pathologic response and favourable RFS. Cytokine and PD-1 levels in plasma increased post-treatment irrespective of response. Additional GES and DSP analysis will be presented.

Conclusions

The 18-mo FU confirms that durable RFS can be achieved with 2 cycles of neoadj IPI+NIVO without any additional adjuvant therapy. Pathologic response remains the strongest marker for RFS. TMB and IFN-y signature might serve as baseline markers identifying pts benefiting from neoadj IPI+NIVO. Neoadj 2 cycles IPI1+NIVO3 should be tested in a randomized phase III study versus adjuvant therapy.

Clinical trial identification

NCT02977052.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

BMS.

Disclosure

E.A. Rozeman: Travel / Accommodation / Expenses: NanoString; Travel / Accommodation / Expenses: MSD. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre. O. Krijgsman: Research grant / Funding (institution): BMS. T.M. Van: Travel / Accommodation / Expenses: NanoString. A.C.J. van Akkooi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: MSD-Merck; Advisory / Consultancy: Merck-Pfizer; Advisory / Consultancy: 4SC. R.A. Scolyer: Advisory / Consultancy: MSD; Advisory / Consultancy: Neracare; Advisory / Consultancy: Novartis. J. Hansson: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Mass Array; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncosec; Advisory / Consultancy: Pierre-Fabre; Advisory / Consultancy: Roche. C.U. Blank: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: GSK; Advisory / Consultancy: GenMap; Advisory / Consultancy: Pierre Fabre; Research grant / Funding (institution): NanoString. All other authors have declared no conflicts of interest.