784O - Adjuvant nivolumab (NIVO) alone or in combination with ipilimumab (IPI) versus placebo in stage IV melanoma with no evidence of disease (NED): Overall survival (OS) results of IMMUNED, a randomized, double-blind multi-center phase II DeCOG trial

Background

The phase 2 study IMMUNED demonstrated significantly longer relapse-free survival (RFS) of NIVO alone or in combination with IPI compared to placebo in stage IV melanoma patients (pts) with NED after surgery or radiotherapy (Zimmer L, et al; Lancet 2020; 395:1558-68). Final RFS and first and final OS data are presented.

Methods

Pts aged ≥18 y with stage IV cutaneous or unknown primary melanoma with NED were randomly assigned 1:1:1 (stratified by trial site, site of metastasis and PD-L1 status) to either NIVO 1 mg/kg + IPI 3 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W (56 patients) or NIVO 3 mg/kg Q2W (n=59) or matching placebo (n=52) for up to 1 year, or until disease recurrence, unacceptable toxicity, or withdrawal of consent. RFS (ITT-population) was the primary endpoint, time to progression, OS and safety secondary endpoints.

Results

At a median follow-up of 49.2 months, NIVO and NIVO+IPI continued to demonstrate superior RFS vs placebo (Table). Overall, 36 OS events had occurred. Median OS was not reached in either group, risk of death was significantly lower for NIVO+IPI vs placebo (HR 0.41, 95% CI, 0.17-0.99) but not for NIVO alone vs placebo (HR 0.75, 95% CI, 0.36-1.56). Most patients of the placebo group with progression (32/42) received anti-PD-1 antibody containing treatment as first subsequent systemic therapy either as crossover or outside the trial. Treatment-related adverse events of grade 3/4 remained largely unchanged (70.9% for NIVO+IPI, 28.6% for NIVO). Table: 784O

HR: hazard ratio; CI: Confidence interval; NR: not reached.

Conclusions

NIVO and NIVO+IPI continued to demonstrate improved RFS in stage IV patients at high risk of recurrence. OS was markedly improved for patients receiving NIVO+IPI compared with placebo. Use of subsequent anti-PD-1 based therapy was high in placebo pts and most likely impacted the OS comparison of NIVO mono vs placebo.

Clinical trial identification

NCT02523313, EudraCT-No. 2014-001167-12.

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

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. 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, Regeneron, Sanofi; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. M. Fluck: Financial Interests, Advisory Board: Novartis, Pfizer, BMS, Roche, Merck. T. Eigentler: Financial Interests, Advisory Board: Bristol Myers Squibb, Novartis, Pierre Fabre, Sanofi, Immunogenics. C. Loquai: Financial Interests, Advisory Board, Speakers fee, travel reimbursement: BMS, MSD, Merck, Novartis, Pierre Fabre, Roche, Sun Pharma, Kyowa Kirin, Biontech, Almirall Hermal, Immunocore, Sanofi. S. Haferkamp: Financial Interests, Advisory Board, Speaker's Bureau: Bristol Myers Squibb, MSD, Pierre Fabre, Novartis. R. Gutzmer: Financial Interests, Advisory Board: Roche, Amgen; Financial Interests, Personal and Institutional, Advisory Board: BMS, MSD, Novartis, Merck Serono; Financial Interests, Invited Speaker: Almirall, 4SC, Immunocore; Financial Interests, Personal and Institutional, Invited Speaker: Sun Pharma, Sanofi, Pierre Fabre; Other, Research Grant: Johnson & Johnson, Amgen, Merck Serono, Sanofi, Kyowa-Kirin, Almirall; Financial Interests, Institutional, Funding: IO Biotech; Non-Financial Interests, Leadership Role: DeCOG/ADO. F. Meier: Financial Interests, Personal, Advisory Board, Speaker's Bureau: Bristol Myers Squibb, MSD, Pierre Fabre, Sanofi; Financial Interests, Personal and Institutional, Advisory Board, Translational Research grant, Speaker's Bureau: Roche, Novartis. P. Mohr: Financial Interests, Personal and Institutional, Advisory Board, Speaker's Bureau: Bristol Myers Squibb, Novartis, MSD; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Roche, Almirall Hermal, Amgen, Bayer, Pierre Fabre, Sanofi; Financial Interests, Personal, Advisory Board, Speakers fee: Merck Serono; Financial Interests, Personal, Advisory Board: Sun Pharma, Beyersdorf. A. Hauschild: Financial Interests, Personal, Advisory Board: BMS, MSD, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi, Novartis, Eisai, Immunocore, Replimune, Seagen; Financial Interests, Personal, Invited Speaker: Merck, Pfizer; Financial Interests, Institutional, Invited Speaker: BMS, MSD, Pierre Fabre, Amgen, Regeneron, Roche, Novartis. J. Simon: Financial Interests, Personal, Advisory Board, Speaker's Bureau: BMS, MSD, Novartis, Pierre Fabre, Philochem. C. Garbe: Financial Interests, Personal, Advisory Board: BMS, CeCaVa, MSD, NeraCare, Novartis, Philogen, Sanofi. J.C. Becker: Financial Interests, Personal, Advisory Board, Consultancy: Almirall Hermal, Boehringer Ingelheim, InProTher; Financial Interests, Personal and Institutional, Other: ICON; Financial Interests, Personal, Advisory Board, Consultancy, Speaker: Merck Serono; Financial Interests, Personal, Advisory Board, Consultancy, Speaker's Bureau: 4SC, Sanofi, Recordati, Pfizer; Financial Interests, Institutional, Research Grant: HTG; Financial Interests, Institutional, Funding: BMS, Alcedis, Sanofi, IQVIA. 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. All other authors have declared no conflicts of interest.