1106O - Overall survival (OS) and safety results from a phase 3 trial of ipilimumab (IPI) at 3 mg/kg vs 10 mg/kg in patients with metastatic melanoma (MEL)

Date 08 October 2016
Event ESMO 2016 Congress
Session Melanoma and other skin tumours
Topics Melanoma and other Skin Tumours
Presenter Paolo Ascierto
Citation Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379
Authors P.A. Ascierto1, M. Del Vecchio2, C. Robert3, A. Mackiewicz4, V. Chiarion-Sileni5, A.M. Arance Fernandez6, H. Schmidt7, C. Lebbe8, L. Bastholt9, O. Hamid10, P. Rutkowski11, C. McNeil12, C. Garbe13, C. Loquai14, B. Dreno15, L. Thomas16, J.J. Grob17, D. Hennicken18, A. Qureshi19, M. Maio20
  • 1Melanoma, Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT
  • 2Medical Oncology, National Cancer Institute, Milano/IT
  • 3Dermatology, Institut Gustave Roussy, Villejuif/FR
  • 4Department Of Diagnostics And Cancer Immunology, Poznan Medical University, PL61614 - Poznan/PL
  • 5Melanoma And Skin Cancer Unit, Istituto Oncologico Veneto IRCCS, Padova/IT
  • 6Medical Oncology, Hospital Clinic, 08036 - Barcelona/ES
  • 7Dept. Of Oncology, Aarhus University Hospital, DK-8000 - Aarhus C/DK
  • 8Dermatology, Hôpital St. Louis, 75010 - Paris/FR
  • 9Oncology, Odense University Hospital, DK-5000 - Odense C/DK
  • 10Research, The Angeles Clinic and Research Institute, Los Angeles/US
  • 11Soft Tissue/bone Sarcoma And Melanoma, Maria Sklodowska-Curie Memorial Cancer Center, 02781 - Warsaw/PL
  • 12Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown/AU
  • 13Dermatology, University Hospital Tübingen, 72074 - Tübingen/DE
  • 14Dermatology, University Medical Center, Mainz/DE
  • 15Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes/FR
  • 16Dermatology, Centre Hospitalier Lyon Sud, Pierre Bénite/FR
  • 17Service De Dermatologie Et Cancérologie Cutanée, Hopital de la Timone, 13885 Marseille CEDEX 05 - Marseille/FR
  • 18Global Biometric Sciences, Bristol-Myers Squibb, Princeton/US
  • 19Global Clinical Research, Bristol-Myers Squibb, Princeton/US
  • 20Medical Oncology And Immunotherapy, University Hospital of Siena, Siena/IT

Abstract

Background

In phase 3 trials, IPI demonstrated an OS benefit at 3 mg/kg as monotherapy in previously treated patients (pts) and at 10 mg/kg in combination with DTIC in untreated pts with MEL. Results of a dose-ranging phase 2 trial suggested longer OS, but a higher incidence of treatment-related grade 3-4 adverse events (AEs), with IPI 10 mg/kg vs. 3 mg/kg. We report the primary results of a randomized, double-blind, phase 3 trial that directly compared the benefit-risk profile of IPI 10 mg/kg vs. 3 mg/kg in MEL pts.

Methods

Pts (N = 727) with untreated or previously treated unresectable stage III or IV melanoma, who had not received prior BRAF or immune checkpoint inhibitors, were randomly assigned 1:1 to IPI 3 mg/kg Q3W x 4 or IPI 10 mg/kg Q3W x 4. Pts were stratified by M substage, prior treatment, and ECOG performance status. Upon disease progression, pts who experienced clinical benefit could be re-induced with IPI at the same dose and schedule. The primary endpoint was OS. Safety was evaluated in all treated pts.

Results

Baseline patient characteristics were balanced between dose groups. Overall, 56.5% of pts received prior systemic therapy. At a minimum follow-up of ∼43 months, IPI 10 mg/kg improved OS vs. IPI 3 mg/kg (Table). Among 726 treated patients, IPI 10 mg/kg vs. 3 mg/kg was associated with higher rates of treatment-related grade 3-5 AEs (34.3% vs. 18.5%), grade 3-5 AEs leading to discontinuation (26.1% vs. 16.0%), and grade 3-5 immune-mediated adverse reactions (33.5% vs. 17.4%). There were 4 (1.1%) deaths in the IPI 10 mg/kg group and 2 (0.6%) in the 3 mg/kg group attributed to study drug toxicity.

IPI 10 mg/kg (N = 365) IPI 3 mg/kg (N = 362)
Median OS, months (95% CI) 15.7 (11.6–17.8) 11.5 (9.9–13.3)
HR (95% CI) 0.84 (0.70–0.99)
P = 0.04
1–Year OS rate (95% CI) 54.3 (49.0–59.3) 47.6 (42.4–52.7)
2–Year OS rate (95% CI) 38.5 (33.4–43.5) 31.0 (26.2–35.8)
3–Year OS rate (95% CI) 31.2 (26.4–36.0) 23.2 (18.9–27.7)

Conclusions

In the first phase 3 trial to directly compare IPI 10 mg/kg with 3 mg/kg in MEL pts who had not received prior BRAF or immune checkpoint inhibitors, IPI 10 mg/kg demonstrated improved OS vs IPI 3 mg/kg, and higher incidence of treatment-related AEs, AEs leading to discontinuation, and immune-mediated adverse reactions.

Clinical trial identification

NCT01515189

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

P.A. Ascierto: Received honoraria from BMS, Roche-Genentech, and GSK, served as a consultant for BMS, Roche-Genentech, MSD, GSK, Ventana, Novartis, Amgen, and received research funding from BMS, Roche-Genentech, Ventana. M. Del Vecchio: Received honoraria from BMS, Roche, GSK, served on advisory board for Roche, received research funding from Roche. C. Robert: Received honoraria from BMS, Merck, GSK, Roche, Novartis, and Amgen, and served as a consultant for BMS, Roche, MSD, and Amgen. V. Chiarion-Sileni: Served as a consultant for BMS, Roche, GSK, MSD, served on a speakers' bureau for BMS, Roche, GSK, and received travel funding from BMS, Roche, GSK, MSD. A.M. Arance Fernandez: Served as a consultant for GSk and Roche, served on a speakers' bureau for GSK, Roche and BMS, and received travel funding from BMS. C. Lebbe: Served on advisory boards for BMS, MSD, Roche, GSK, and Novartis. L. Bastholt: Served on advisory boards for BMS, MSD, Roche, and GSK. O. Hamid: Served as a consultant for BMS, Novartis, Roche, Merck, Merck Serono, Pfizer, Genentech, and Amgen, and served on a speakers' bureau for BMS, Genentech, and Novartis. P. Rutkowski: Honoraria from BMS, Roche, Novartis, MSD, GSK, Consultant for BMS, Amgen, Roche, MSD, speakers' bureau for Pfizer, MSD, Novartis, his institution received research funding from BMS, and received travel funding from Novartis. C. McNeil: Received travel funding from BMS. C. Garbe: Honoraria from BMS, MSD, Roche, Novartis, and Amgen, consultant for BMS, MSD, Roche, Novartis, and Amgen, research funding from BMS, Roche, Novartis, and travel funding from BMS, MSD, Roche, Novartis, and Amgen. C. Loquai: Served as a consultant for BMS, Roche, MSD, and Amgen, served on a speakers' bureau for BMS, Roche and MSD, and received travel funding from BMS, Roche, and MSD. B. Dreno: Received research funding from BMS. J.J. Grob: Served as a consultant for BMS, GSK, Novartis, Roche, Merck, and Amgen, served on a speakers' bureau for GSK, Roche, BMS, received research funding from Roche and BMS, and received travel funding from Roche. D. Hennicken, A. Qureshi: Employed by BMS M. Maio: Honoraria from BMS, MSD, Roche, GSK, and MedImmune, consultant for BMS, MSD, Roche, GSK, and MedImmune, research funding from MedImmune and BMS, and travel funding from BMS, MSD, Roche, GSK, and MedImmune. All other authors have declared no conflicts of interest.