804P - Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: 5-year results of the EORTC 1325-MG/Keynote-054 double-blinded phase III trial

Background

We conducted the randomized phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. At 3.5-year (yr) median follow-up, pembrolizumab improved recurrence-free survival (RFS) (hazard ratio [HR] 0.59; 95% CI 0.49-0.70, P<0.0001) and distant metastasis-free survival (DMFS) (HR 0.60, 95% CI 0.49-0.73, P<0.0001) as compared to placebo (Eggermont, TLO 2020).

Methods

Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). Between Aug-2015 until Nov-2016, 1019 pts were randomized to pembrolizumab 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses or until disease recurrence or unacceptable toxicity. The co-primary endpoints were RFS in the intention-to-treat (ITT) overall population and in pts with PD-L1-positive tumors. DMFS was a secondary and progression/recurrence-free survival 2 (PRFS2, time from randomization until the 2nd disease recurrence, a progression of the 1st recurrence, or death) an exploratory endpoint.

Results

Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. By Jan 17, 2022, at approximately 5-yr median follow-up, 532 RFS, 470 DMFS and 382 PRFS2 events were reported. Pembrolizumab compared with placebo significantly prolonged RFS, DMFS and PRFS2 in the ITT population and in the PD-L1+ subgroup (N=853). Consistent improvements were observed across subgroups, in particular by AJCC staging and BRAF-mutation status. Table: 804P

*: 5-yr rate **: stratified by stage at randomization.

Conclusions

At approximately 5-yr median follow-up, adjuvant pembrolizumab provided a clinically meaningful improvement in RFS, DMFS, and PRFS2 in resected high-risk stage III melanoma pts.

Clinical trial identification

EudraCT, 2014-004944-37; NCT02362594.

Editorial acknowledgement

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

A.M.M. Eggermont: Financial Interests, Personal, Advisory Role: Agenus, Biocad, BioInvent, Bio-NTech, BMS, CatalYm, Ellipses, Galecto, GSK, IO Biotech, ISA Pharmaceucals, Merck/MSD, Nektar, Novartis, Pfizer, SAiRoPA, Sellas, SkylineDx, TigaTx, TTxDiscovery; Financial Interests, Personal, Invited Speaker: Biocad, BMS, Merck/MSD, Novartis; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Advisory Board: GSK, Novartis, Pfizer; Financial Interests, Personal, Stocks/Shares: SkylineDx, SAiRoPA; Non-Financial Interests, Personal, Officer: European Academy Cancer Sciences, German Cancer Aid. M. Kicinski: Financial Interests, Institutional, Research Grant: MSD/Merck, BMS, Pierre Fabre. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Expert Testimony: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Uniti Cars, co-founder Immagene BV; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, NanoString, 4SC. M. Mandala: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. V.G. Atkinson: Financial Interests, Personal, Advisory Board: BMS, MSD, Nektar, Novartis, Pierre Fabre, QBiotics; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Limbic; Financial Interests, Personal, Other, Travel Support: BMS. S. Dalle: Financial Interests, Institutional, Advisory Board: MSD, BMS; Financial Interests, Institutional, Research Grant: BMS, MSD. A.M. Haydon: Financial Interests, Personal, Speaker’s Bureau: Novartis, Merck; Financial Interests, Personal, Advisory Board: Novartis, Merck, Pierre Fabre, BMS. A. Meshcheryakov: Financial Interests, Personal, Invited Speaker: Amgen, Bayer AG, Bristol Myers Squibb, BIOCAD, Eli Lilly, Merck, SERVIER, Takeda Pharmaceuticals, Eisai, AstraZeneca, Sanofi-Aventis; Financial Interests, Personal, Advisory Board: Amgen, Bayer AG, AmgenBristol Myers Squibb, Biocad, Eli Lilly, Merck, Servier, Takeda Pharmaceuticals, Eisai, AstraZeneca, Sanofi-Aventis; Financial Interests, Personal and Institutional, Research Grant: Sanofi-Aventis, AstraZeneca, Merck Sharp & Dohme. M.S. Carlino: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre, Roche, IDEAYA Biosciences, Sanofi, Merck Serono, Regeneron Pharmaceuticals, QBiotics, Nektar. 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; 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 don’t 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 don’t receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Principal 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.S. Puig Sarda: Financial Interests, Institutional, Research Grant: Almirall, ISDIN, La Roche Posay; Financial Interests, Personal, Advisory Role: ISDIN, Almirall, La Rohe Posay, Sanofi, Sunpharma, Pfizer, Roche, Regeneron; Financial Interests, Personal, Invited Speaker: ISDIN, La Roche Posay, Pfizer, Roche, Regeneron, BMS, Sunpharma; Financial Interests, Personal, Advisory Board: Roche, Sanofi, Sunpharma, Almirall, ISDIN, Pfizer, Novartis. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; 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, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. P. Lorigan: Financial Interests, Personal, Advisory Role: BMS, MSD, Novartis, Nektar, Medis Diagnosis, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis, Pierre Fabre; Financial Interests, Personal, Stocks/Shares: Supportive Care; Financial Interests, Institutional, Research Grant: BMS, Pierre Fabre; Non-Financial Interests, Personal, Leadership Role, Chair: EORTC Melanoma Group; Non-Financial Interests, Personal, Leadership Role, Past Chair: Melanoma Focus Charity . D. Grebennik: Financial Interests, Personal, Full or part-time Employment: Merck. N. Ibrahim: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck, GSK. S. Suciu: Financial Interests, Institutional, Funding: MSD/Merck, Pierre Fabre, BMS. C. Robert: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer. All other authors have declared no conflicts of interest.