LBA8_PR - Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: a randomized, double-blind, phase...

Date 11 September 2017
Event ESMO 2017 Congress
Session Presidential Symposium III
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Jeffrey Weber
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors J. Weber1, M. Mandala2, M. Del Vecchio3, H. Gogas4, A.M. Arance5, L.C. Cowey6, S. Dalle7, M. Schenker8, V. Chiarion-Sileni9, I. Márquez-Rodas10, J. Grob11, M. Butler12, M.R. Middleton13, M. Maio14, V. Atkinson15, P. Queirolo16, V. de Pril17, A. Qureshi17, J. Larkin18, P.A. Ascierto19
  • 1Perlmutter Cancer Center, NYU Langone Health, 10016 - New York/US
  • 2Oncology, Papa Giovanni XIII Hospital, Bergamo/IT
  • 3Medical Oncology, National Cancer Institute, Milan/IT
  • 4Oncology, University of Athens, Athens/GR
  • 5Oncology, Hospital Clinic de Barcelona, Barcelona/ES
  • 6Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas/US
  • 7Oncology, Hospices Civils de Lyon, Pierre Bénite/FR
  • 8Oncology, Oncology Center sf. Nectarie Ltd., Craiova/RO
  • 9Oncology, Oncology Institute of Veneto IRCCS, Padua/IT
  • 10Medical Oncology, Hospital Gregorio Marañón, Madrid/ES
  • 11Medical Oncology, Hospital de la Timone, Marseille/FR
  • 12Oncology, Princess Margaret Cancer Centre, Toronto/CA
  • 13Oncology, Churchill Hospital, University of Oxford, OX3 7LE - Oxford/GB
  • 14Center For Immuno-oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena/IT
  • 15Oncology, Gallipoli Medical Research Foundation and Princess Alexandra Hospital, and University of Queensland, Queensland/AU
  • 16Oncology, IRCCS AOU San Martino - IST, 16132 - Genova/IT
  • 17Global Clinical Research - Oncology, Bristol-Myers Squibb, Princeton/US
  • 18Oncology, The Royal Marsden Hospital, London/GB
  • 19Oncology, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT

Abstract

Background

NIVO and IPI are immune checkpoint inhibitors approved for advanced melanoma. IPI is also approved in the US for resected stage III melanoma, based on a phase 3 trial demonstrating an improvement in recurrence-free survival (RFS). We report the first results of a phase 3 trial designed to evaluate NIVO vs IPI for resected stage III/IV melanoma at high risk of recurrence.

Methods

In this randomized, double-blind trial, eligible patients (pts) included those ≥15 yrs of age who underwent complete resection of stage IIIb/c or IV melanoma. 906 pts were randomized (stratified by stage and PD-L1 status) 1:1 to receive NIVO 3 mg/kg (n = 453) every 2 wks or IPI 10 mg/kg (n = 453) every 3 wks for 4 doses, then every 12 wks (from week 24) for up to 1 yr, disease recurrence, or unacceptable toxicity. The primary endpoint was RFS in the intent-to-treat population.

Results

Overall, 34%/47%/19% of pts had stage IIIb/IIIc/IV; 32%, ulcerated primary; 48%, macroscopic lymph node involvement; and 42%, BRAF mutation. At a median follow-up of 18.5 mo, NIVO significantly improved RFS vs IPI (Table). Results from prespecified subgroup analyses demonstrated consistent hazard ratios favoring NIVO.

Table:

LBA8_PR

NIVO (N = 453)IPI (N = 453)
18-mo RFS rates (95% CI)66.4% (61.8–70.6)52.7% (47.8–57.4)
Median RFSNot reachedNot reached
HR (95% CI)0.65 (0.51–0.83)
Log-rankP 100 days post-IPI.

Conclusions

NIVO as adjuvant therapy significantly improved RFS vs IPI for pts with stage III/IV melanoma at high risk of recurrence and demonstrated a superior safety profile. Acknowledgement: The co-senior authors for this abstract are Dr. J. Larkin and Dr. P.A. Ascierto.

Clinical trial identification

NCT02388906

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

J. Weber: Celldex, Ichor Medical Systems, cCam Biotherapeutics, Lion Biotechnologies, Pieris Pharmaceuticals, Altor BioScience, Bristol-Myers Squibb, Merck, Genentech, Roche, Amgen, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, Abbvie, Eisai, CytomX Therapeutics, Nektar, Novartis, Medivation: consulting or advisory role; Bristol-Myers Squibb, GlaxoSmithKline, Daiichi Sankyo, Pieris Pharmaceuticals, cCam Biotherapeutics, Lion Biotechnologies, Roche, Celldex, Amgen, Merck, AstraZeneca, Genentech, Novartis: travel, accommodations, expenses; Named on a patent submitted by Moffitt Cancer Center for an ipilimumab biomarker; Altor BioScience, Celldex, CytomX Therapeutics: stock and other ownership interests; Bristol-Myers Squibb, Merck, Genentech, Abbvie, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Eisai, Altor BioScience, Altor BioScience, Amgen, Roche, Ichor Medical Systems, Celldex, cCam Biotherapeutics, Pieris Pharmaceuticals, CytomX Therapeutics, Nektar, Novartis, Medivation: honoraria; Bristol-Myers Squibb, Merck, Gla. M. Mandala: Roche: personal fees, grant; BMS, MSD, Novartis: personal fees. M. Del Vecchio: BMS: personal fees, honoraria; Roche: personal fees, honoraria, advisory board, research funding; GSK: personal fees, honoraria. H. Gogas: Roche, Amgen MSD, BMS, Novartis: consulting or advisory role, research funding; BMS, Roche, MSD: travel accommodations, expenses. A.M. Arance: GSK, Roche, personal fees, Consultant, speakers\' bureau; BMS: personal fees & non-financial support, Speakers\' bureau, travel funding. L.C. Cowey: BMS, Genentech: grant, personal fees, consultant, Speaker, Research funding; Merck, GSK: grant, consultant, Research funding. S. Dalle: BMS: research grants and travel expenses; BMS, MSD, Novartis, Roche: principal investigator V. Chiarion-Sileni: BMS, Roche, GSK: personal fees, consulting, speakers\' bureau, travel; MSD: personal fees, consulting, travel. I. Márquez-Rodas: Novartis, Roche, MSD, BMS: honoraria; Novartis, Roche, MSD, BMS, Amgen, Bioncotech: consulting or advisory role; MSD, BMS, Amgen: travel, accommodations, expenses. J-J. Grob: BMS: personal fees, consultant, speakers\' bureau, research funding; GSK: personal fees, consultant, speakers\' bureau; Novartis: personal fees, consulting; Roche: personal fees, non-financial support, consulting, speakers\' bureau, research funding, travel; Merck, Amgen: personal fees, consulting M. Butler: Bristol Myers Squib, EMD Serono, Immunocore, Immunovaccine: personal fees, advisory boards; Merck: grant, personal fees, advisory boards, grant support for clinical trial. M.R. Middleton: Amgen, Bristol-Myers Squibb, Clovis, GlaxoSmithKline, Immunocore (uncompensated), Merck, Roche (all compensated): consulting or advisory role; Amgen, AstraZeneca, Bristol-Myers Squibb, Clovis, Eisai, GlaxoSmithKline, Immunocore, Medimmune, Merck, Pfizer, Roche, Vertex: research funding; Merck, Roche: travel, accommodations, expenses. M. Maio: BMS, Roche, MedImmune, MSD, GSK: honoraria, consulting or advisory role, travel, accommodations, expenses; BMS, MedImmune: research funding. V. Atkinson: BMS, MSD, Novartis: honoraria, consulting or advisory role, speakers\' bureau, travel, accommodations, expenses. P. Queirolo: Roche, MSD, BMS, Novartis: personal fees. V. de Pril, A. Qureshi: employment – Bristol-Myers Squibb and stock/ownership – Bristol-Myers Squibb J. Larkin: BMS, MSD, Novartis, Pfizer: research funding; BMS, MSD, Pfizer, Eisai, GSK, Roche: travel, accommodations, expenses. P.A. Ascierto: Bristol-Myers Squibb, Roche-Genentech: grant, personal fees, honoraria, consultant, institutional research funding; GSK: personal fees, honoraria, consultant; MSD, personal fees, consultant; Ventana: grant, consultant, institutional research funding; Novartis: Consultant. All other authors have declared no conflicts of interest.