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Proffered paper session - Melanoma and other skin tumours

3062 - OpACIN-neo – A Multicenter Phase 2 Study to identify the Optimal neo-Adjuvant Combination scheme of Ipilimumab (IPI) and Nivolumab (NIVO).

Date

22 Oct 2018

Session

Proffered paper session - Melanoma and other skin tumours

Presenters

Christian Blank

Authors

E.A. Rozeman1, A.M. Menzies2, B.A. van de Wiel3, C. Adhikari4, K. Sikorska5, O. Krijgsman6, H. Eriksson7, C. Bierman3, L. Grijpink-Ongering5, M. Gonzalez2, A. Broeks3, A.D. Guminski8, A.J. Spillane9, W.M.C. Klop10, R.P.M. Saw9, R.A. Scolyer11, A.C.J. van Akkooi12, J. Hansson7, G.V. Long2, C.U. Blank1

Author affiliations

  • 1 Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2 Medical Oncology, Melanoma Institute Australia, University of Sydney, 2060 - North Sydney/AU
  • 3 Department Of Pathology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 4 Pathology, Melanoma Institute Australia, University of Sydney, 2060 - North Sydney/AU
  • 5 Department Of Biometrics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 6 Department Of Molecular Oncology And Immunology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 7 Department Of Oncology-pathology, Karolinska Institutet, Stockholm/SE
  • 8 Medical Oncology, Royal North Shore Hospital, 2065 - St Leonards/AU
  • 9 Surgical oncology, Melanoma Institute Australia, University of Sydney, 2060 - North Sydney/AU
  • 10 Head And Neck Surgery And Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 11 Pathology, Royal Prince Alfred Hospital, 2050 - Camperdown/AU
  • 12 Surgical oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
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Abstract 3062

Background

Outcomes of high risk stage III melanoma patients (pts) are poor, with a 5-year overall survival (OS) rate of <50%. Adjuvant (adj) IPI improved 5-year recurrence-free survival (RFS) and OS, and adj NIVO or pembrolizumab improved RFS further. OpACIN, a phase 1b study of neoadjuvant (neoadj) vs adj IPI + NIVO, demonstrated a pathological response rate (pRR) of 78% in the neoadj arm with an increased expansion of tumor-resident TCR clones vs adj. None of the pts with a pathologic response have yet relapsed. However, toxicity was high with 90% grade 3/4 immune-related adverse events (irAEs). This raised the question whether alternative scheduling of neoadj IPI + NIVO may reduce toxicity, but preserve efficacy.

Methods

In this multi-center phase 2 trial (OpACIN-neo) pts with resectable stage III melanoma were randomized 1:1:1 to arm A: 2x IPI 3mg/kg + NIVO 1mg/kg Q3W; arm B: 2x IPI 1mg/kg + NIVO 3mg/kg Q3W; and arm C: 2x IPI 3mg/kg Q3W followed immediately by 2x NIVO 3mg/kg Q2W. Complete lymph node dissection was scheduled at week 6. Primary endpoints were grade ≥3 irAEs within the first 12 weeks, radiologic RR (RECIST 1.1), and pRR (<50% viable tumor cells). Major inclusion criteria were: ≥1 measurable lymph node metastases (RECIST 1.1), no in-transit metastases in the last 6 months, and normal LDH.

Results

86 patients were evaluable; 30 pts in arm A and B, and 26 in arm C. Median follow up was 7.7 months. On advice of the DSMB, arm C was closed earlier due to toxicity. Grade ≥3 irAEs occurred in 40%, 20%, 50% of pts in arm A, B, and C, respectively. Radiologic RR was 60%, 60%, and 42%, whilst pRR was 80% (43% pCR), 77% (57% pCR), and 68% (24% pCR). None of the pts with a pathologic response have relapsed, while 9/21 pts with no pathologic response (pNR) have relapsed. Two pts have died, one (arm A, pNR) of melanoma and one (arm A, pCR) due to complications after an immune-related encephalitis 9.5 months after start of therapy. Baseline IFN-signature biomarker analyses will be presented.

Conclusions

Neoadj IPI 1 mg/kg + NIVO 3 mg/kg is less toxic than the standard dosing regimen. The high response rate was preserved, making this schedule an attractive candidate to be tested against adj PD-1 blockade in a phase 3 study.

Clinical trial identification

NCT02977052

Editorial Acknowledgement

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