LBA42 - Distant metastasis-free survival of neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in resectable, macroscopic stage III melanoma: The NADINA trial

Background

At first interim analysis, with a median FU of 10 months, the phase 3 NADINA trial demonstrated a significantly improved event-free survival (EFS) of neoadjuvant (neoadj) ipilimumab (IPI) plus nivolumab (NIVO) as compared to adjuvant (adj) NIVO in resectable, macroscopic stage III melanoma (1-year EFS 83.7% vs 57.2%, HR 0.32 [99.9% CI 0.15-0.66, p<0.0001]). Here, we report the updated EFS and distant metastasis-free survival (DMFS).

Methods

Patients (pts) with resectable, macroscopic stage III melanoma were randomized to receive neoadj IPI 80mg + NIVO 240mg (2x, q3w) followed by therapeutic lymph node dissection (TLND; 212 pts) or to undergo upfront TLND followed by adj NIVO (480mg, 12x, q4w; 211 pts). In the neoadj arm, subsequent adj treatment was omitted in case of a major pathologic response (MPR; ≤10% viable tumor). EFS and DMFS were analyzed using a cox regression model. Melanoma stage (ypTNM) was assessed according to AJCC staging system (8^th edition).

Results

Median FU was 15.4 months at data cutoff on 12 July 2024. At 18 months, EFS was improved for the neoadj compared to the adj arm (80.8% vs 53.9%, adjusted HR 0.32 [95% CI 0.22-0.48], nominal p

Conclusions

Neoadj IPI + NIVO in resectable, macroscopic stage III melanoma results in improved DMFS and EFS as compared to adj NIVO. This EFS-benefit is observed within stage IIIB- and IIIC melanoma. High RFS and DMFS rates were observed for pts with a MPR or radiological CR or PR.

Clinical trial identification

NCT04949113.

Editorial acknowledgement

Legal entity responsible for the study

The Netherlands Cancer Institute.

Funding

Bristol Myers Squibb; Australian Government Grant (National Health and Medical Research Council [NHMRC; MRFF2007157]).

Disclosure

A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. R.A. Scolyer: Financial Interests, Institutional, Advisory Role: F. Hoffmann-La Roche Ltd, MetaOptima Technology Inc., Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen Inc, Bristol Myers Squibb, Myriad Genetics, GSK, IO Biotech ApS, SkylineDX B.V.. B. van de Wiel: Non-Financial Interests, Advisory Role, no activities in last two years: BMS. R.P.M. Saw: Financial Interests, Personal, Invited Speaker: Bristol Myers Squib, Novartis; Financial Interests, Personal, Advisory Board: MSD, Novartis, Qbiotics; Financial Interests, Personal, Advisory Board, for MelaSeq-38: Australian Clinical Labs; Financial Interests, Personal, Other, On Faculty, support of University of Sydney salary: Melanoma Institute Australia. W. Van Houdt: Financial Interests, Institutional, Invited Speaker: Amgen, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: Belpharma, Sanofi, MSD; Financial Interests, Personal, Other, travel grant: Novartis; Financial Interests, Institutional, Local PI: BMS; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Funding: Sirius. N. Maher: Financial Interests, Personal, Invited Speaker: The Melanoma Dermatology Trust, Australia, Dermpedia/Dermatopathology Consultations LLC, Sydney Cancer Partners. M. Boers-Sonderen: Financial Interests, Personal, Other: Pierre Fabre. G. Hospers: Financial Interests, Institutional, Advisory Board: BMS, MSD; Financial Interests, Institutional, Research Grant: BMS, Seerave Foundation. M.S. Carlino: Financial Interests, Personal, Advisory Board, Consultant Advisor: MSD, BMS, Novartis, Amgen, Oncosec, Merck, Sanofi, Ideaya, Pierre-Fabre, Eisai, Nektar, Regeneron. J.W. de Groot: Non-Financial Interests, Institutional, Member of Board of Directors: Board member of Nederlandse Vereniging voor Medische Oncologie. E. Kapiteijn: Financial Interests, Institutional, Advisory Board: Delcath, Lilly; Financial Interests, Institutional, Invited Speaker: Immunocore; Financial Interests, Institutional, Coordinating PI: BMS, Pierre-Fabre, Delcath, Novartis. K. Suijkerbuijk: Financial Interests, Institutional, Advisory Board: Novartis, BMS, AbbVie, Pierre Fabre, MSD; Financial Interests, Institutional, Other, honoraria for Safety Review Committee: Sairopa; Financial Interests, Institutional, Research Grant: Novartis, TigaTx, Bristol Myers Squibb, Philips. 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: Pfizer; 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. 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 Myer Squibb sponsored studies and don't receive any renumeration for this: Bristol Myer 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 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 Myer Squibb sponsored trial and I do not receive renumeration for this: Bristol Myer Squibb. A.A.M. Van der Veldt: Financial Interests, Institutional, Advisory Role: Bristol Myers Squib, MSD, Sanofi, Pierre Fabre, Eisai, Ipsen, Pfizer, Novartis Roche; Financial Interests, Institutional, Advisory Board: Sairopa. 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 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. 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, pending patent: WO 2021/177822 A1. All other authors have declared no conflicts of interest.