LBA3 - 30 months relapse-free survival, overall survival, and long-term toxicity update of (neo)adjuvant ipilimumab (ipi) + nivolumab (nivo) in macroscopi...

Date 15 December 2018
Event ESMO Immuno-Oncology Congress 2018
Session Mini Oral session
Topics Melanoma
Immunotherapy
Presenter Elisa Rozeman
Citation Annals of Oncology (2018) 29 (suppl_10): x39-x43. 10.1093/annonc/mdy511
Authors E.A. Rozeman1, K. Sikorska2, B.A. van de Wiel3, L.F. Fanchi4, O. Krijgsman4, H.V. van Thienen1, L.M. Pronk2, A. Broeks3, L. Grijpink-Ongering2, S. Ter Meulen5, A. Bruining6, W.M.C. Klop5, H. van Tinteren2, D. Peeper4, J.B.A.G. Haanen1, A.C.J. van Akkooi5, T.N. Schumacher7, C.U. Blank1
  • 1Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2Department Of Biometrics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 3Department Of Pathology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 4Department Of Molecular Oncology And Immunology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1006 BE - Amsterdam/NL
  • 5Surgical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 6Department Of Radiology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 7Department Of Molecular Oncology And Immunology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL

Abstract

Background

Outcome of high-risk stage III melanoma patients (pts) has been poor, with a 5-year overall survival (OS) rate of < 50%. Adjuvant IPI improved 5-year relapse-free survival (RFS) and OS and adjuvant (adj) anti-PD1 improved RFS further. Neoadjuvant (neoadj) IPI + NIVO has been shown in 3 investigator-initiated trials to induce high pathologic response rates. While standard dosing regimen of IPI 3mg/kg + NIVO 1mg/kg has been too toxic for broader application, OpACIN-neo identified 2 courses IPI 1mg/kg + NIVO 3mg/kg as well tolerated and effective scheme to proceed to phase 3. Pathologic response was a good predictor for early outcome (none of the pts relapsed), but longer follow-up (FU) data are missing so far.

Methods

Between August 2015 and October 2016, 20 high risk, stage IIIB/IIIC melanoma pts with palpable nodal disease were included in the phase 1b feasibility OpACIN trial. Pts were randomized to receive IPI 3mg/kg plus NIVO 1mg/kg, either adj 4 courses, or split 2 courses neoadj and 2 adj. Pathological response was reviewed by a blinded pathologist, response was defined as < 50% viable tumor cells. The study was not powered to compare both arms, all efficacy endpoints are descriptive.

Results

After a median FU of 31.6 months (minimum 23.5 months FU of pts alive) none of the 7 pts that achieved a pathologic response in the neoadj arm have relapsed. Two non-responding pts in the neoadj arm have relapsed, and 4 pts in the adj arm. 1 pt died in the neoadj arm and 3 in the adj arm. Estimated 30 months RFS rates were 80% for the neoadj arm and 60% for the adj arm and 30 months OS rates were 90% and 67%, respectively. Of the 18 (90%) pts that had developed one or more grade 3-4 adverse events, all recovered to ≤ grade 1, except for grade 2 endocrine toxicities needing hormonal suppletion therapy that are ongoing in 8 (50%) of 16 pts alive.

Conclusions

OpACIN was the first trial investigating neoadj IPI + NIVO in pts with macroscopic stage III melanoma, thus having the longest FU. None of the pts with a pathologic response has relapsed, suggesting that this could become a primary read-out for subsequent neoadj immunotherapy trials and a surrogate marker for RFS and OS.

Editorial acknowledgement

Clinical trial identification

NCT02437279.

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

BMS.

Disclosure

E.A. Rozeman: Travel support: MSD, NanoString. H.V. van Thienen: Travel support: Roche. D. Peeper: Research support: BMS. J.B.A.G. Haanen: Fees to NKI for advisory roles: BMS, MSD, Roche, Neon Therapeutics, Immunocore, Novartis, AstraZeneca/MedImmune, Pfizer, Ipsen; Grants to NKI: BMS, Merck, Novartis, Neon Therapeutics. A.C.J. van Akkooi: Personal fees for advisory role: Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer; Grants: Amgen, Novartis, all outside the submitted work. T.N. Schumacher: Consultant: Adaptive Biotechnologies, AIMM Therapeutics, Amgen, Neon Therapeutics, Scenic Biotech; Grant/research support: Merck, BMS, Merck KGaA; Stockholder: AIMM Therapeutics, Neon Therapeutics. C.U. Blank: Personal fees for advisory roles: MSD, BMS, Roche, GSK, Novartis, Pfizer, Lilly; Grants: BMS, Novartis. All other authors have declared no conflicts of interest.