2801 - Adjuvant nivolumab (NIVO) versus ipilimumab (IPI) in resected stage III/IV melanoma: 3-year efficacy and biomarker results from the phase 3 CheckMate 238 trial

Background

The phase III study CheckMate 238 demonstrated improved relapse-free survival (RFS) with NIVO 3 mg/kg vs IPI 10 mg/kg in patients (pts) with resected stage III/IV melanoma. Sustained efficacy benefit at 24 mo of follow-up with NIVO vs IPI was previously reported. Here we present a 36mo analysis of efficacy and biomarker data from this study.

Methods

Pts aged ≥ 15 y with completely resected stage IIIB/C or IV melanoma were randomized 1:1 to receive NIVO (3 mg/kg Q2W; N = 453) or IPI (10 mg/kg Q3W for 4 doses; Q12W thereafter; N = 453) for ≤ 1 y or until disease recurrence/unacceptable toxicity. RFS was the primary endpoint; exploratory endpoints included distant metastases-free survival (DMFS) in pts with stage III disease and potential biomarkers of efficacy.

Results

With 36 mo of follow-up, NIVO continued to demonstrate superior RFS vs IPI (HR, 0.68; P < 0.0001; 3-y RFS rates, 58% vs 45% and 188/453 vs 239/453 pts with events, respectively). Prespecified subgroup analyses demonstrated a consistent pattern similar to that of the 24-mo analysis, with HRs favoring NIVO (Table). DMFS analysis also continued to favor NIVO (Table). High levels of all biomarkers analyzed (interferon-gamma gene expression signature, tumor mutational burden, and CD8+ T-cell infiltration by immunohistochemistry) showed an association with improved RFS for both NIVO and IPI. Median RFS (mo; 24-mo follow-up) by high vs low values for each biomarker for NIVO was 30.8 vs 24.1, not reached (NR) vs 30.8, and 30.8 vs 24.9, respectively; and for IPI was NR vs 15.9, NR vs 18.3, and NR vs 13.8, respectively.Table:

1310O

Stratified results for ITT population, unstratified results for subgroups.

Per American Joint Committee on Cancer 7th edition.

Includes pts with PD-L1 status categorized as indeterminate.

Conclusions

With 36 mo of follow-up, NIVO continued to demonstrate superior efficacy over IPI in pts with stage III/IV melanoma at high risk of recurrence across pt subgroups. Additional analyses using composite scoring of biomarker combinations will be presented.

Clinical trial identification

NCT02388906.

Editorial acknowledgement

Wendy Sacks, PhD, and Cara Hunsberger, MS, of StemScientific, an Ashfield company, funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

J.S. Weber: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celldex; Honoraria (self), Advisory / Consultancy: Ichor Medical Systems; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: cCam Biotherapeutics; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lion Biotechnologies; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pieris Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: Altor BioScience; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: GSK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: CytomX Therapeutics; Honoraria (self), Advisory / Consultancy: Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Medivation; Honoraria (self), Advisory / Consultancy: Sellas Life Sciences; Honoraria (self), Advisory / Consultancy: WindMIL; Non-remunerated activity/ies, named on a patent for an ipilimumab biomarker: Moffitt Cancer Center; Non-remunerated activity/ies, named on a patent for a PD-1 antibody biomarker: Biodesix; Shareholder / Stockholder / Stock options: Biond; Honoraria (self): AbbVie; Research grant / Funding (institution): InCyte; Research grant / Funding (institution): Astellas Pharma. M. Del Vecchio: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pierre Fabre. M. Mandala: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Honoraria (self), Advisory / Consultancy: MSD Oncology. H. Gogas: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD Oncology; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre. A.M. Arance: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck. S. Dalle: Shareholder / Stockholder / Stock options, Full / Part-time employment: Sanofi Pasteur; Advisory / Consultancy, Research grant / Funding (institution): MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca. C.L. Cowey: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Regeneron; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Array; Research grant / Funding (institution): Amgen. M. Schenker: Research grant / Funding (self), Research grant / Funding (institution): BMS; Research grant / Funding (self), Research grant / Funding (institution): Roche; Research grant / Funding (self), Research grant / Funding (institution): Novartis; Research grant / Funding (self), Research grant / Funding (institution): Lilly; Research grant / Funding (self), Research grant / Funding (institution): Bayer; Research grant / Funding (self), Research grant / Funding (institution): Amgen; Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Research grant / Funding (self), Research grant / Funding (institution): AbbVie; Research grant / Funding (self), Research grant / Funding (institution): Astellas; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self), Research grant / Funding (institution): Merck Serono; Research grant / Funding (self), Research grant / Funding (institution): Mylan; Research grant / Funding (self), Research grant / Funding (institution): Bioven. J.J. Grob: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Pfizer. V. Chiarion-Sileni: Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Merck Serono; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: MSD. I. Marquez-Rodas: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Incyte; Advisory / Consultancy, Travel / Accommodation / Expenses: Bioncotech; Advisory / Consultancy: Pierre Fabre. M.O. Butler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Immunovaccine; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: Genzyme; Honoraria (self): Roche; Research grant / Funding (self): Takara Bio. M. Maio: Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Merck. M.R. Middleton: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: CytomX Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): RigonTEC; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Newlink Genetics; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: BiolineRx; Advisory / Consultancy: Johnson and Johnson; Advisory / Consultancy: Merck; Honoraria (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Vertex; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Replimune; Research grant / Funding (institution): Array Biopharm; Research grant / Funding (institution): TC Biopharm; Research grant / Funding (institution): Regeneron. T. Tang: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. A. Saci: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. V. De Pril: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. M. Lobo: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS; Shareholder / Stockholder / Stock options, Full / Part-time employment: Advaxis Immunotherapies. J.M.G. Larkin: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy: GSK; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: Sectra; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Achilles Therapeutics; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boston Biomedical; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Imugene; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: iOncologi; Advisory / Consultancy: Kyocera; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Nektar; Honoraria (self), Advisory / Consultancy: Vitaccess; Honoraria (self): Secarna; Honoraria (self): Kymab; Research grant / Funding (institution): Covance; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): AVEO. P.A. Ascierto: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Incyte; Advisory / Consultancy: Genmab; Advisory / Consultancy: Newlink Genetics; Advisory / Consultancy: MedImmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Idera; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Immunocore.