787O - Adjuvant immunotherapy with nivolumab (NIVO) versus observation in completely resected Merkel cell carcinoma (MCC): Disease-free survival (DFS) results from ADMEC-O, a randomized, open-label phase II trial

Background

MCC is a rare, immunogenic but aggressive skin cancer. Even after complete resection and radiation relapse rates are high. PD-1/PD-L1 immune checkpoint inhibitors (ICI) showed clinical benefit in locally advanced MCC. ADMEC-O is the first trial to investigate the efficacy/safety of adjuvant PD-1 blockade by ICI in completely resected MCC, i.e. in a situation with no systemic Standard of Care.

Methods

This multicenter phase 2 trial enrolled MCC patients (pts) (any stage, ECOG PS 0-1) with tumor lesions completely resected within 12 weeks prior to a 2:1 randomization to either NIVO 480 mg Q4W for up to 1 year, or observation, stratified by stage of disease (AJCC I/II vs. III/IV), age (<65 vs. ≥65 years) and gender. DFS was the primary endpoint, overall survival (OS) and adverse events (AE) secondary endpoints. This planned interim analysis was triggered when the Last Patient In was followed for at least 1 year.

Results

From 03/2017 until 08/2020 179 pts (NIVO, n=118; observation, n=61) were enrolled from 20 centers (ITT population; 62% male, 68% ≥65 years, 67% stage III/IV), with baseline characteristics well balanced across both arms. At this interim analysis with a median follow-up of 24.3 months (IQR 19.2-33.4), all pts had ended treatment. DFS rates at 12 and 24 months favored NIVO with 87.9% vs 78.5%, and 86.9% vs 74.3%, respectively. OS results are not yet mature. Treatment was well tolerated, with 41% of NIVO pts and 31% of pts in the observation group experiencing grade 3/4 AEs; only 5% of pts discontinued due to adverse events. No treatment-related deaths were reported. Table: 787O

* HR: hazard ratio for the median provided by a univariate Cox model; CI, Confidence interval; NR, not reached

Conclusions

In this first randomized trial for MCC, a hazard ratio for DFS of 0.56 (95% CI 0.28-1.15) in favor of NIVO was observed at a median follow-up of 2 years, suggesting clinical benefit in this unmet medical need. Remarkably, the spontaneous course of MCC was considerably better than historical data would have suggested.

Clinical trial identification

NCT02196961; EudraCT-No. 2013-000043-78.

Editorial acknowledgement

Writing assistance by Dr Markus Hartmann, Ecc-Oncology, Trier, Germany.

Legal entity responsible for the study

University Hospital Essen, represented by Prof. Dr. Dirk Schadendorf Hufelandstr. 55, D-45147 Essen, Germany.

Funding

Bristol Myers Squibb.

Disclosure

J.C. Becker: Financial Interests, Personal, Advisory Board, Consultancy: Almirall Hermal, Boehringer Ingelheim, InProTher, 4SC; Financial Interests, Personal, Advisory Board, Speaker's Bureau, Consultancy: Merck Serono; Financial Interests, Personal, Advisory Board, Consultancy, Speaker's Bureau: Sanofi, Recordati, Pfizer; Financial Interests, Personal, Other, DSMB Member: ICON; Financial Interests, Personal, Funding: HTG; Financial Interests, Institutional, Research Grant: Merck Serono, Bristol Myers Squibb, Sanofi; Financial Interests, Institutional, Funding: Alcedis, IQVIA. S. Ugurel: Financial Interests, Personal, Advisory Board, Speaker's Bureau: Merck Serono, Bristol Myers Squibb, MSD; Financial Interests, Personal, Other, Travel Support: Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, Merck Serono. U. Leiter-Stoppke: Financial Interests, Personal, Advisory Board, Speaker's Bureau: Novartis, Roche, MSD, Sanofi, Almirall Hermal, Sun Pharma. F. Meier: Financial Interests, Personal, Invited Speaker, Advisory Board: Novartis, Roche, BMS, MSD, Pierre Fabre, Sanofi. R. Gutzmer: Financial Interests, Personal, Invited Speaker: Roche, 4SC, Immunocore; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Invited Speaker, Funding: MSD, Novartis, Pierre Fabre, Sanofi, Merck Serono, Sun Pharma; Financial Interests, Personal, Invited Speaker, Funding: Amgen, Almirall Hermal; Financial Interests, Personal, Funding: Johnson & Johnson, Kyowa Kirin; Financial Interests, Institutional, Funding: IO Biotech; Financial Interests, Institutional, Research Grant: Pfizer; Other, Personal and Institutional, Leadership Role: ADO & DeCOG. S. Haferkamp: Financial Interests, Personal, Invited Speaker, Advisory Board: BMS, MSD, Pierre Fabre, Novartis. L. Zimmer: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, MSD, Sunpharma, Pierre Fabre, Sanofi; Financial Interests, Personal, Other, Travel Support: Bristol Myers Squibb, MSD, Sunpharma, Pierre Fabre, Sanofi, Novartis, Amgen; Financial Interests, Personal, Invited Speaker: Novartis, MSD, Pierre Fabre, Roche; Financial Interests, Personal and Institutional, Research Grant: Novartis; Non-Financial Interests, Member: German Cancer Society, Dermatologic Cooperative Oncology Group. E. Livingstone: Financial Interests, Personal, Advisory Board: Novartis, BMS, Sanofi, Sun Pharma, Recordati; Financial Interests, Personal, Invited Speaker: Novartis, BMS, Medac; Financial Interests, Personal, Other, Innvator´s Circle: Pierre Fabre; Financial Interests, Personal, Expert Testimony: MSD; Non-Financial Interests, Principal Investigator: BMS, Novartis, Regeneron, MSD, Philogen, 4SC, Biontech; Non-Financial Interests, Member: DeCOG, DKG. T. Eigentler: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pierre Fabre, Sanofi, Immunogenics. A. Hauschild: Financial Interests, Personal, Advisory Board: BMS, MSD, Philogen, Pierre Fabre, Regereron, Roche, Sanofi, Novartis, Eisai, Immunocore, Replimune, Seagen; Financial Interests, Personal, Invited Speaker: MerckPfizer; Financial Interests, Institutional, Invited Speaker: BMS, MSD, Pierre Fabre, Amgen, Regeneron, Roche, Novartis. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, sanofi, MSD, Sunpharma, Almirall, Roche, Amgen, GSK, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, Pierre Fabre, Sunpharma, GSK; Financial Interests, Institutional, Advisory Board: Novartis, BMS, Immunocore, Nektar, Philogen; Financial Interests, Institutional, Research Grant: BMS, Sunpharma; Financial Interests, Institutional, Invited Speaker: Philogen, BMS, Genentech, Immunocore, Immunocore, 4SC, Novartis, BioNTech, Idera, Iovance, Nektar, Pierre Fabre, Regeneraon, Sanofi; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. P. Mohr: Financial Interests, Personal and Institutional, Invited Speaker, Advisory Board: BMS, Novartis, MSD; Financial Interests, Personal, Invited Speaker, Advisory Board: Roche, Almirall Hermal, Amgen, Merck Serono, Bayer, Pierre Fabre, Sanofi; Financial Interests, Personal, Advisory Board: Sun Pharma, Beyersdorf; Non-Financial Interests, Personal and Institutional, Advisory Role: Onkowissen; Other, Personal, Member: DKG & DeCOG. M. Fluck: Financial Interests, Personal, Invited Speaker, Advisory Board: BMS, Novartis, Roche, MSD, Pierre Fabre, Sanofi; Non-Financial Interests, Personal, Member: DKG & DeCOG. I. Thomas: Financial Interests, Personal, Advisory Board, Investigator Role (Clinical trials): BMS; Financial Interests, Personal, Funding, Investigator Role (Clinical trials): Pfizer, MSD; Financial Interests, Personal and Institutional, Funding, Investigator Role (Clinical trials): Amgen, Novartis, Sanofi, 4SC, AstraZeneca, Biontech, Roche (Genentech), Curevac, HUYA, Incyte, Idera, Iovance, Infla-Rx, Cerpass, Kartos, Nektar, Philogen, Pierre Fabre, Regeneron; Financial Interests, Institutional, Funding, Investigator Role (Clinical trials): Leo, UCB, Replimune; Non-Financial Interests, Personal, Member: EADO & DKG & ADO. I. Grimmelmann: Financial Interests, Personal and Institutional, Invited Speaker, Advisory Board: BMS, Novartis; Financial Interests, Personal, Advisory Board: Almirall Hermal, Pierre Fabre, Sanofi Genzyme; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker, Advisory Board: Sun Pharma; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Institutional, Funding: Pfizer. S. Eckhardt: Financial Interests, Personal, Full or part-time Employment: Alcedis . D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi, Merck, Novartis, BMS, MSD, 4SC, Nektar; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Roche, Merck Serono, Immunocore, 4SC, Pierre Fabre, Sanofi/Regeneron, Array Biopharma, Pfizer, Philogen, Nektar, Sandoz, Neracare; Financial Interests, Institutional, Research Grant: Novartis, BMS, MSD, Array/Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, BMS, MSD, Pierre Fabre, Sanofi, Roche, Philogen, 4SC, Nektar; Non-Financial Interests, Invited Speaker: EORTC-MG. All other authors have declared no conflicts of interest.