1077MO - Adjuvant nivolumab v placebo in stage IIB/C melanoma: 3-year results from CheckMate 76K

Background

Patients (pts) with resected stage IIB/C melanoma are at high risk of recurrence, similar to resected stage IIIB disease pts. CheckMate 76K (NCT04099251) demonstrated a significant reduction in the risk of recurrence or death with nivolumab (NIVO) vs placebo (PBO) in pts with completely resected stage IIB/C melanoma, leading to widespread regulatory approval. Updated data with 3-y follow-up are presented here.

Methods

Pts aged ≥ 12 y without evidence of residual disease following resection were stratified by tumor (T) category and randomized 2:1 to receive IV NIVO 480 mg or PBO Q4W for 12 mo. The primary endpoint (EP) was recurrence-free survival (RFS); other EPs were distant-metastasis free survival (DMFS), safety, and progression-free survival 2 (PFS2). Baseline tissue was analyzed for emergent biomarkers.

Results

A total of 790 pts were randomized 2:1 to NIVO or PBO. At the 3-y follow-up (median 34.2 mo [NIVO] and 33.9 mo [PBO]), recurrence events occurred in 22% v 34% of pts, respectively, including distant recurrence in 11% v 17%; distant recurrence sites included lung (8% v 12%), lymph node (4% v 8%), liver (3% v 3%), and brain (2% v 4%). NIVO continued to demonstrate improved RFS and DMFS v PBO (Table). RFS benefit was also observed across predefined subgroups, including T category (HR [95% CI]: T3b, 0.59 [0.37–0.94]; T4a, 0.57 [0.31–1.01]; T4b, 0.65 [0.44–0.96]). Fewer NIVO pts received subsequent systemic therapy (12%) v PBO (27%), and pts receiving adjuvant NIVO had sustained benefit v PBO beyond first progression (PFS2; Table). There were no new safety signals. At 24 mos, number needed to treat with NIVO to avoid 1 recurrence was 8 (95% CI, 6–18), and number needed for 1 additional grade 3-4 TRAE was 8 (95% CI, 6–12). Table: 1077MO

aNIVO vs PBO (stratified Cox proportional hazards model).

Conclusions

3-y follow-up results support the positive benefit–risk profile of adjuvant NIVO as a treatment option for pts with resected stage IIB/C melanoma. The benefit was observed across all subgroups and confirms NIVO as an effective adjuvant treatment. Biomarker data to be presented.

Clinical trial identification

NCT04099251.

Editorial acknowledgement

Writing and editorial assistance were provided by Melissa Kirk and Michele Salernitano of Ashfield Medcomms.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

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. M. Del Vecchio: Financial Interests, Personal, Advisory Board, Advisor and Consultant and Invited Speaker: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Immunocore; Non-Financial Interests, Principal Investigator, Clinical Trials: Bristol Myers Squibb, Merck Sharp & Dohme, Immunocore. C. Hoeller: Financial Interests, Personal, Invited Speaker, Advisory Boards, Speaker: Amgen; Financial Interests, Personal, Advisory Board, Advisory Boards, Speaker: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi; Financial Interests, Personal, Advisory Board: Almirall; Financial Interests, Institutional, Coordinating PI: Amgen, Bristol Myers Squibb, Pierre Fabre, Roche; Financial Interests, Institutional, Local PI: Merck Sharp & Dohme, Novartis; Non-Financial Interests, Member, Board Member: European Association of Dermato-Oncology (EADO); Non-Financial Interests, Member: EORTC Melanoma Group. J.S. Weber: Financial Interests, Personal, Advisory Board, Ad Boards: BMS; Financial Interests, Personal, Advisory Board: Merck, GSK, Incyte, Genentech, Pfizer, Biond, OncoC4, AstraZeneca, Regeneron, ImCheck, Novartis; Financial Interests, Personal, Stocks/Shares: Biond, Evaxion, Instil Bio, OncoC4; Financial Interests, Personal, Royalties: Moffitt Cancer Center; Financial Interests, Institutional, Local PI: BMS, Regeneron; Financial Interests, Institutional, Coordinating PI: Merck, Novartis; Non-Financial Interests, Principal Investigator: Moderna, BMS; Non-Financial Interests, Member: ASCO. J.J. Grob: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Roche, Pierre Fabre, Novartis, Pfizer, Sanofi, Philogen, Iteos Therapeutics, SunPharma; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pierre Fabre, Sanofi; Financial Interests, Personal, Steering Committee Member: Novartis; Financial Interests, Institutional, Research Grant: Pierre Fabre. P. Mohr: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Merck Sharp & Dohme, Merck Sharp & Dohme, Novartis, GSK, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Sharp & Dohme, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis; Non-Financial Interests, Principal Investigator: Bristol Myers Squibb, Merck Sharp & Dohme, Regeneron, Sanofi, Novartis, Sun Pharma. S. Grabbe: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, SUN Pharma, Klinge Pharma, Kyowa-Kirin, UCB; Financial Interests, Personal, Other, Travel Support: BMS, MSD, Novartis, SUN Pharma, Klinge Pharma, Kyowa-Kirin, UCB; Financial Interests, Institutional, Research Grant: Novartis, Pierre Fabre; Financial Interests, Personal, Principal Investigator: Anaveon AG, BioNTech SE, Parexel International (IRL) Limited, Agenus, Inc, HUYABIO International, LLC, I0 BIOTECH APS, Regeneron Pharmaceuticals, Inc, Novartis Pharma GmbH, Syneos Health UK Limited, Bristol Myers Squibb International Corporation, Genentec, Inc. C. Dutriaux: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, Novartis, Pierre Fabre, Sun Pharma, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Sun Pharma, Sanofi; Financial Interests, Personal, Other, Support for attending meetings and/or travel: BMS, MSD; Financial Interests, Personal, Advisory Board, Support for attending meetings and/or travel: Novartis, Pierre Fabre, Sun Pharma, Sanofi. V. Chiarion Sileni: Financial Interests, Personal, Other, Travel, registration, and accommodation to attend ASCO annual meetings: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre, Immunocore; Financial Interests, Personal, Other, Medical Congress Travel, registration and accommodation: Sanofi. J. Mackiewicz: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Novartis, Roche, Pierre Fabre; Other, Other, Travel grant: Bristol Myers Squibb, MSD, Novartis, Roche, Pierre Fabre. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. P. Arenberger: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Sanofi. G. Quereux: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Novartis, Pierre Fabre Dermatologie. T. Meniawy: Financial Interests, Personal, Advisory Board: BMS, GSK, MSD, AstraZeneca, Eisai; Financial Interests, Institutional, Local PI: BMS, MSD, GSK, Moderna; Financial Interests, Institutional, Coordinating PI: AstraZeneca. 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. J. Taube: Financial Interests, Institutional, Research Funding: BMS, Akoya Biosciences; Financial Interests, Personal, Stocks/Shares: Akoya Biosciences; Financial Interests, Personal, Advisory Board: BMS, Merck, AstraZeneca, Compugen, Elephas, Moderna, Genentech, Regeneron, Lunaphore, Akoya Biosciences. A. Nassar: Financial Interests, Personal, Full or part-time Employment, Clinical Trial Physician for the study submitted: Bristol Myers Squibb. W. Wang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J.M. Kirkwood: Financial Interests, Personal, Advisory Board: Ankyra Therapeutics, Axio Research, LLC; Financial Interests, Personal, Advisory Board, Institutional study lead for trial 76k: Bristol Myers Squibb; Financial Interests, Personal, Other, SAB member and global study PI: CytomX Therapeutics; Financial Interests, Personal, Other, Collaborator utilizing technology of DermTech in two trials; past consensus conference organizer: DermTech; Financial Interests, Personal, Advisory Board, SAB member, now no longer involved in the this: Onctura; Financial Interests, Personal, Advisory Board, Institutional study lead and study coauthor: Iovance Biotherapeutics; Financial Interests, Personal, Advisory Board, DSMB chair: IQVIA; Financial Interests, Personal, Advisory Board, SAB member no longer involved since 2022: Istari Oncology, OncoCyte Corporation, PathAI, Pfizer, Inc, Scopus BioPharma, Inc; Financial Interests, Personal, Advisory Board, SAB member 2022 no longer involved: Jazz Pharmaceuticals, Inc; Financial Interests, Personal, Other, Institutional study lead: Lytix Biopharma AS; Financial Interests, Personal, Advisory Board, SAB member, no longer involved since 2022: Magnolia Innovation, Inc, Merck; Financial Interests, Personal, Advisory Board, SAB member no longer involved as SAB member since 2022: Natera, Inc; Financial Interests, Personal, Advisory Role, Study steering committee member and coauthor: Novartis Pharmaceuticals; Financial Interests, Personal, Advisory Board, KOL input provided 2022, no longer involved: Piper Sandler & Co; Non-Financial Interests, Personal, Advisory Board, SAB member and consultant, without financial remuneration: PyrOjas Corporation; Financial Interests, Personal, Advisory Board, Institutional Study lead: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Advisory Board, DSMB chairman for Ignyte trial: Replimune; Financial Interests, Personal, Advisory Board, Institutional Study Lead for TAK 573 no longer involved in study since 2023: Takeda; Non-Financial Interests, Personal, Advisory Board, Advisor, unremunerated: Valar Labs, Inc; Financial Interests, Institutional, Other: Amgen, Inc, Bristol Myers Squibb; Financial Interests, Institutional, Other, Cease to exist in 2022; purchased by Regeneron: Checkmate Pharmaceuticals; Financial Interests, Institutional, Other, SAB member until 2022 no longer active: Harbour BioMed; Financial Interests, Institutional, Other, Trial participant until 2022 no longer active: Immvira Pharma Co; Financial Interests, Institutional, Other, Trial participant until 2023 but not since: Immunocore, Ltd; Financial Interests, Institutional, Other, Institutional Study Lead for C14401 but no longer active since 2023: Iovance Biotherapeutics; Financial Interests, Institutional, Other, No longer an existing company (now called Iovance): Lion Biotechnologies, Inc; Financial Interests, Institutional, Other, Institutional Study participant 2022-2023 but not since 2023 for trial HCC 22-143: Lytix Biopharma AS; Financial Interests, Institutional, Other, Steering committee member for Combi-Ad trial: Novartis Pharmaceuticals; Financial Interests, Institutional, Other, Institutional study lead 2021-2023 but no longer active since 2023: Takeda; Financial Interests, Institutional, Other, Institutional Study lead but no longer active since 2023: Verastem, Inc; Financial Interests, Personal, Member of Board of Directors, Chair of IMWG sponsored by AIM since 2004 to present: AIM at Melanoma.