1112PD - PD-L1 expression as a biomarker for nivolumab (NIVO) plus ipilimumab (IPI) and NIVO alone in advanced melanoma (MEL): A pooled analysis

Date 10 October 2016
Event ESMO 2016 Congress
Session Melanoma and other skin tumours
Topics Skin Cancers
Translational Research
Melanoma
Basic Principles in the Management and Treatment (of cancer)
Presenter Georgina Long
Citation Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379
Authors G.V. Long1, J. Larkin2, P.A. Ascierto3, F..S. Hodi4, P. Rutkowski5, V. Sileni6, J. Hassel7, C. Lebbe8, A.C. Pavlick9, J. Wagstaff10, D. Schadendorf11, R. Dummer12, D. Hogg13, J.B.A.G. Haanen14, P. Corrie15, C. Hoeller16, C. Horak17, J. Wolchok18, C. Robert19
  • 1Medical Oncology, Melanoma Institute Australia, 2065 - Sydney/AU
  • 2Department Of Medical Oncology, Royal Marsden Hospital, SW3 6JJ - London/GB
  • 3Melanoma, Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT
  • 4Oncology, Dana-Farber Cancer Institute, Boston/US
  • 5Oncology, MSC Memorial Cancer Centre and Institute Maria Sklodowska-Curie, 02-781 - Warsaw/PL
  • 6Oncology, Istituto Oncologico Veneto, Padova/IT
  • 7Oncology, University Hospital Heidelberg, Heidelberg/DE
  • 8Dermatology, Hôpital St. Louis, 75010 - Paris/FR
  • 9Department Of Medicine, New York University School of Medicine, New York/US
  • 10South West Wales Cancer Institute, South West Wales Cancer Institute Singleton Hospital, Sketty, SA2 8QA - Swansea/GB
  • 11Cancer, University Hospital of Essen, 45147 - Essen/DE
  • 12Department Of Dermatology, University Hospital Zurich, 8091 - Zurich/CH
  • 13Department Of Medical Oncology And Hematology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
  • 14Department Of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 15Oncology Centre, Addenbrooke's Hospital University of Cambridge Hospitals, CB2 0QQ - Cambridge/GB
  • 16Dpt. Of Dermatology And Dermatooncology, Medizinische Universitaet Wien (Medical University of Vienna), 1090 - Vienna/AT
  • 17Clinical Biomarkers, BMS, Princeton/US
  • 18Ludwig Center, Memorial Sloan Kettering Cancer Center, New York/US
  • 19Oncology, Gustave Roussy and Paris-Sud University, Villejuif/FR

Abstract

Background

NIVO + IPI and NIVO showed superior clinical activity vs IPI in a phase 3 trial of MEL patients (pts), irrespective of PD-L1 tumor expression. Among pts with high PD-L1 expression (≥5%), median progression-free survival (mPFS) was similar between NIVO + IPI and NIVO, but overall response rate (ORR) was higher with NIVO + IPI. We describe PD-L1 as a biomarker for NIVO + IPI and NIVO efficacy across phase 2 (CheckMate 069) and phase 3 (CheckMate 066 and 067) trials.

Methods

Treatment-naïve pts (N = 832) with MEL received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4 or NIVO 3 mg/kg Q2W, followed by NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. Tumor tissue from primary or metastatic sites, obtained at screening, was assessed for PD-L1 expression using a validated Dako immunohistochemistry assay. Minimum pt follow-up was 18 months (mos). Survival data remain immature.

Results

The proportion of pts with PD-L1 expression ≥5% was 26% (92/358) for NIVO + IPI and 29% (139/474) for NIVO. Pt characteristics were similar between PD-L1 subgroups, although fewer pts had LDH > ULN in the PD-L1 ≥5% subgroup. Among pts with PD-L1 expression ≥5%, mPFS of NIVO + IPI was not reached (NR) and was 22.0 mos for NIVO alone (hazard ratio [HR]: 0.99, 95% CI: 0.66─1.46). For pts with low to no PD-L1 (

Conclusions

While pts with ≥5% PD-L1 tumor expression have better efficacy outcomes, those with

Clinical trial identification

NA

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

G.V. Long: Served as a consultant for GSK, Roche, Novartis, BMS, Amgen, and Merck, and received honoraria from Merck, GSK, Roche. J. Larkin: Institution received research funding from Pfizer, BMS, Novartis, MSD. P.A. Ascierto: Received honoraria from BMS, Roche-Genentech, and GSK, served as a consultant for BMS, Roche-Genentech, MSD, GSK, Ventana, Novartis, and Amgen, and institution received research funding from BMS, Roche-Genentech, and Ventana. F.S. Hodi: Served as a consultant from BMS (non-paid), institution received research funding from BMS, and his institution has a patent pending for immune target. P. Rutkowski: Honoraria from BMS, Roche, Novartis, MSD, and GSK, consulted for BMS, Amgen, Roche, and MSD, participated in speaker's bureau for Pfizer, MSD and Novartis, institution received research funding from BMS, and received travel support from Novartis. V. Sileni: Served as a consultant for Roche, BMS, GSK, and MSD, participated in speaker's bureau for Roche, BMS and GSK, and received travel support from Roche, GSK, MSD, and BMS. J. Hassel: Received honoraria from BMS, GSK, Roche, MSD, and Amgen, served as a consultant for Amgen and GSK, participated in speaker's bureau for BMS, GSK, Roche, MSD, and Amgen, and received travel support from Amgen and BMS. C. Lebbe: Dr. Lebbe served on advisory boards for BMS, MSD, Roche, GSK, Novartis. A.C. Pavlick: Served as a consultant for BMS and Amgen, and participated in speaker's bureau for BMS. J. Wagstaff: Served as a consultant for BMS. D. Schadendorf: Honoraria: Roche, GSK, Amgen, Novartis, BMS, MSD; consultant: Roche, GSK, Amgen, Novartis, BMS, MSD; speakers bureau: Roche, GSK, Amgen, Novartis, BMS, MSD; institutional research funding: MSD, and travel from Roche, GSK, Amgen, Novartis, BMS, MSD. R. Dummer: Paid honoraria from Roche, BMS, GSK, MSD, and Novartis, served as a consultant for Roche, BMS, GSK, MSD, and Novartis, received research funding from Roche, BMS, GSK, MSD, and Novartis. D. Hogg: Served as a consultant for BMS, Roche, Novartis and GSK. J.B.A.G. Haanen: Served as a consultant for MSD, Roche and Pfizer, received research funding from BMS and GSK. P. Corrie: Paid honoraria from Roche, BMS, GSK, and Celgene, served as a consultant for Roche, BMS, Merck, GSK, and Celgene, and received travel support from BMS, Merck and Roche. C. Hoeller: Paid honoraria from BMS, MSD, Roche, Novartis, Amgen and GSK, served as a consultant for BMS, MSD, Roche and Amgen, received research funding from BMS, MSD, Roche, Novartis, and GSK. C. Horak: Employed by BMS and owns stock in BMS. J. Wolchok: Honoraria: EMD Serono, Janssen Oncology; consultant: BMS, Merck, MedImmune, Ziopharm, Polynoma, Polaris, Jounce, GSK; institutional research funding: BMS, MedImmune, GSK, Merck; co-investor in patent for DNA vaccines of cancer in animals; travel: BMS. C. Robert: Paid honoraria from BMS, Merck, GSK, Roche, Novartis and Amgen, served as a consultant for BMS, Merck, GSK, Roche, Novartis, and Amgen.