1095P - Pembrolizumab versus placebo after a complete resection of high-risk stage III melanoma: 7-year results of the EORTC 1325-MG/Keynote-054 double-blind phase III trial

Background

Based on earlier results from our trial, pembrolizumab became a standard adjuvant treatment following a resection of high-risk stage III melanoma. Since late recurrences may occur, long-term data is of key importance.

Methods

Adults with AJCC-7 stage IIIA and a lymph node metastasis >1 mm or IIIB/C without in-transit metastases were randomized 1:1 to receive pembrolizumab 200 mg every 3 weeks or placebo. Treatment continued until a patient received 18 doses or experienced a recurrence or unacceptable toxicity. The co-primary endpoints were recurrence-free survival (RFS) in the overall intention-to-treat (ITT) population and in patients with PD-L1-positive tumors. Distant metastasis-free survival (DMFS) was a secondary and progression/recurrence-free survival 2 (PRFS2, time from randomization until the 2nd recurrence, a progression of the 1st recurrence, or death) an exploratory endpoint. The clinical cut-off date for this analysis was January 3, 2024. The overall survival analysis is planned after 380 deaths or 10 years from the randomization of the last patient, whichever occurs first.

Results

Between Aug-2015 and Nov-2016, 1019 patients were randomized. Overall, 15%, 46% and 39% of patients had stage IIIA, IIIB and IIIC, respectively. The median follow-up was approximately 7 years. Pembrolizumab prolonged RFS, DMFS and PRFS2 compared with placebo. Consistent improvements were observed by BRAF-mutation and PD-L1 status. Overall, 286 patients had died. Table: 1095P

CI: confidence interval; HR: hazard ratio.

Conclusions

This long-term follow-up data shows that treatment with pembrolizumab following a resection of high-risk stage III melanoma results in a clinically meaningful improvement of RFS, DMFS and PRFS2 as compared with placebo.

Clinical trial identification

EudraCT: 2014-004944-37; NCT02362594.

Editorial acknowledgement

Legal entity responsible for the study

Merck.

Funding

Merck.

Disclosure

A.M.M. Eggermont: Financial Interests, Personal, Advisory Board: Agenus, BioInvent, Boehringer Ingelheim Ingelheim, BioNTech, Brenus, CatalYm, Galecto, Egle, Eikon Therapeutics, Imcheck, IO Biotech, ISA Pharmaceuticals, Merck&Co, MSD, Pfizer, Pierre Fabre, IQVIA, Pierre Fabre, GenOway, Sairopa, Scancell, SkylineDX, Scorpion, TigaTX, Trained Therapeutics DIscovery; Financial Interests, Personal, Stocks/Shares: IO Biotech, Sairopa, SkylineDX. M. Kicinski: Financial Interests, Institutional, Research Grant: MSD, BMS; Financial Interests, Institutional, Funding: Pierre Fabre, Immunocore, JnJ. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Advisory Board: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Immagene; Financial Interests, Personal, Stocks/Shares, intention to develop IFN signature algorithm: Signature Oncology; Financial Interests, Institutional, Coordinating PI: NanoString, BMS, Novartis, 4SC; Other, Other, pending patent: WO 2021/177822 A1. M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L, IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. V.G. Atkinson: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, QBiotics; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Limbic; Financial Interests, Personal, Other, Travel Support: BMS; Financial Interests, Personal, Other, Travel support: Pierre Fabre; Financial Interests, Personal, Other, Advisory Board: Immunocore. S. Dalle: Financial Interests, Institutional, Advisory Board: MSD, BMS; Financial Interests, Personal, Stocks/Shares, Spouse Sanofi employee and stock owner: Sanofi; Financial Interests, Institutional, Research Grant: BMS, MSD, AstraZeneca. A.M. Haydon: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis. A. Meshcheryakov: Other, Other, Sponsor of scientific conference: Janssen. M.A. Khattak: Financial Interests, Personal, Advisory Board: Moderna; Financial Interests, Personal, Invited Speaker: MSD. M.S. Carlino: Financial Interests, Personal, Advisory Board, Consultant Advisor: MSD, BMS, Novartis, Amgen, Oncosec, Merck, Sanofi, Ideaya, Pierre Fabre, Eisai, Nektar, Regeneron. S.K. Sandhu: Financial Interests, Institutional, Advisory Board, I have served on advisory boards for BMS. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Bristol Myer Squib; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for MSD. The e contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Merck Sharp and Dohme; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for AstraZeneca. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: AstraZeneca; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for Novartis. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Novartis; Financial Interests, Institutional, Advisory Board, I have served on an advisory board for Merck Serono. The contracts for my service are set up with the institution and funds go into a research fund at the Peter MacCallum Cancer Centre: Merck Serono; Financial Interests, Institutional, Research Grant, My institution receives grant funding to run an investigator initiated trial that I lead: Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, Merck Sharp and Dohme; Financial Interests, Institutional, Funding, Pfizer are providing funding to my institution for the conduct of an investigator initiated clinical trial: Pfizer; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Janssen sponsored studies and don't receive any renumeration for this: Janssen; Non-Financial Interests, Principal Investigator, I am a principal investigator on several Novartis sponsored studies and dont receive any renumeration for this: Novartis; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Genentech sponsored studies and don't receive any renumeration for this: Genentech; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Bristol Myers Squibb sponsored studies and don't receive any renumeration for this: Bristol Myers Squibb; Non-Financial Interests, Other, I serve on the Independent Safety and Data Monitoring committee for 2 of Novartis sponsored studies and dont receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Priincipal Investigator for several AstraZeneca sponsored studies and am not remunerated for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for several Janssen sponsored trials and i do not receive compensation for this: Janssen; Non-Financial Interests, Other, I serve on the steering committee for one AstraZeneca sponsored trial and I do not receive compensation for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for one Genentech sponsored trials and I do not receive compensation for this: Genentech; Non-Financial Interests, Other, I serve on the steering committee for a Bristol Myers Squibb sponsored trial and I do not receive renumeration for this: Bristol Myers Squibb. S. Puig Sarda: Financial Interests, Personal, Advisory Board: Almirall, Isdin, Sanofi, MSD, Pfizer, Novartis, SunPharma, la Roche Posay, Regeneron; Financial Interests, Personal, Invited Speaker: Almirall, Avene, Isdin, Sanofi, Regeneron, Pierre Fabre, SunPharma, la Roche Posay, Cantabria, Eucerin, Bioderma; Financial Interests, Institutional, Other, grants: Almirall; Financial Interests, Institutional, Other, grants: la Roche Posay; Financial Interests, Institutional, Funding: Leo Pharma, Cantabria; Financial Interests, Institutional, Research Grant: la Roche Posay; Financial Interests, Institutional, Other, prototypes: Damae medica; Financial Interests, Institutional, Other, Research collaboration: Canfield; Non-Financial Interests, Member of Board of Directors, spin off of the Hospital Clinic and IDIBAPS: Athena Tech. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role.Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. P. Lorigan: Financial Interests, Personal, Advisory Board, ASCO2023 participation, travel support: MSD; Financial Interests, Personal, Advisory Board: NeraCare; Financial Interests, Institutional, Research Grant: BMS, Pierre Fabre; Non-Financial Interests, Other, invited speaker: Melanoma Focus charity; Non-Financial Interests, Other, invited session chair: SMR Edinburgh 2022; Non-Financial Interests, Leadership Role, current 2023 Chairman of group: EORTC Melanoma Group; Non-Financial Interests, Other, clinical research committee: CRUK. D. Grebennik: Financial Interests, Institutional, Stocks/Shares: Merck. C. Krepler: Financial Interests, Personal, Full or part-time Employment: Merck& Co; Financial Interests, Personal, Stocks/Shares: Merck& Co. S. Suciu: Financial Interests, Institutional, Funding: MSD/Merck. C. Robert: Financial Interests, Personal, Other, Consultancy fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer, Sun Pharma. All other authors have declared no conflicts of interest.