1110O - Immunogenicity and safety of the prame cancer immunotherapeutic in metastatic melanoma: phase I/II dose escalation study

Date 29 September 2012
Event ESMO Congress 2012
Session Melanoma
Topics Immunotherapy
Skin cancers
Presenter Ralf Gutzmer
Authors R. Gutzmer1, L. Rivoltini2, E. Levchenko3, A. Testori4, J. Utikal5, P.A. Ascierto6, B. Salaun7, N. Vanhoutte8, M. Gillet9, V. Brichard10
  • 1Dermatology And Allergy, Hannover Medical School, 30449 - Hannover/DE
  • 2Unit Of Immunotherapy Of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3Thoracic Oncology, Petrov Research Institution of Oncology, 197758 - St. Petersburg/RU
  • 4Melanoma Division, EUROPEAN INSTITUTE OF ONCOLOGY, 20141 - Milan/IT
  • 5Skin Cancer Unit, German Cancer Research Center, Heidelberg, Germany And Department Of Dermatology, Venereology And Allergology, University Medical Center Mannheim, Ruprecht-karl University Of Heidelberg, Mannheim, Germany, German Cancer Research Center, 68135 - Mannheim/DE
  • 6Melanoma, Cancer Immunotherapy And Innovative Therapies, Istituto Nazionale Tumori Fondazione “G. Pascale”, 80131 - Napoli/IT
  • 7R&d Dap Cancer, GlaxoSmithKline Biologicals, 1330 - Rixensart/BE
  • 8Immunotherapeutics, GlaxoSmithKline Biologicals, 1330 - Rixensart/BE
  • 9Global Vaccine Development, GlaxoSmithKline Biologicals, 1330 - Rixensart/BE
  • 10Immunotherapeutics Bu, GlaxoSmithKline Biologicals, 1330 - Rixensart/BE



Patients (pts) with metastatic melanoma have a poor prognosis. The PRAME tumor antigen, expressed at high frequency in different cancers and at lower levels in a limited number of normal cells, offers an attractive target for active immunization. This open-label, dose-escalation phase I/II study aimed at determining the optimal dose of PRAME immunotherapeutic (PRAME recombinant protein (recPRAME) with AS15 immunostimulant) by evaluating its safety and immunogenicity in pts with advanced melanoma.


Pts with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 injections of recPRAME (20 µg, 100 µg, and 500 µg) with AS15 (fixed dose) over approximately 4 years. Adverse events (AEs), including pre-defined dose-limiting toxicity (DLT), were recorded throughout the study. The anti-PRAME humoral and cellular responses were evaluated post-dose 4 by ELISA and flow cytometry (PRAME-specific T-cells producing both IFNγ and TNFα), respectively.


66 pts were treated in the study (20 pts received 20 µg recPRAME, 24 pts received 100 µg recPRAME and 22 pts received 500 µg recPRAME). AEs considered by the investigator to be causally related were mostly grade 1/2, 2 pts reported grade 3 AEs, and 1 serious AE causally related to PRAME administration was reported. 2 DLTs were recorded in 2 pts (cohorts 2 and 3; post-dose 6 and 8) but no maximum tolerated dose was reached. Humoral and cellular immunological results are shown in table 1. No cellular response for CD8+ T-cells was detected.


PRAME cancer immunotherapeutic was well-tolerated and induced similar humoral and cellular responses in all 3 cohorts. Based on these results, a phase II was initiated to further evaluate the clinical activity, safety and immunogenicity of the PRAME immunotherapeutic containing 500 µg recPRAME.

Immunogenicity post-dose 4 (ATP population).

Cohort (recPRAME dose) 1 (20 µg) 2 (100 µg) 3 (500 µg)
Humoral responders, n/N* 13/13 13/13 17/17
CD4+ T-cell responders, n/N* (%) 7/9 (78%) 7/11 (64%) 11/15 (73%)
CD8+ T-cell responders, n/N* (%) 0/8 (0%) 0/9 (0%) 0/8 (0%)

number of patients enrolled into each group; * number of patients with pre and post-vaccination results; n, number of responders; ATP, according-to-protocol


GSK Biologicals


R. Gutzmer: Roche Pharma, BMS, GSK, Novartis, MSD/Essex, Celgene, Lilly, EISAI, Astra-Zeneca, Vical, Cytavis, Centocor, Genta, SwedishOrphan, Philogen, Amgen, Almirall-Hermal, Merck Serono (Clin. studies, Research, Lectures, Advisory honoraria, Meetings).

L. Rivoltini: Participation to one single GSK Advisory Board on MEK/BRAF inhibitors in Melanoma.

A. Testori: I declare to have a consultant or advisory relationship with Bristol Meyers Squibb, AMGEN, GlaxoSmithKline advisory boards and I received honoraria from them. I have other remuneration to disclose: travel expenses refunded by Oncovision and IGEA.

J. Utikal: I dońt have any financial interest in products or processes involved in this research abstract. I dońt own GSK stocks. I served as a member on an advisory of GSK and Roche in the past time.

P.A. Ascierto: Consultant for MSD; Advisory role for BMS, MSD, Roche-Genetech, GSK, Amgen, Celgene, Medimmune, Novartis; received honoraria from BMS, MSD, and Roche-Genentech.

B. Salaun: Currently employed by GSK Biologicals as a scientist.

N. Vanhoutte: Employee of GSK Biologicals.

M. Gillet: Employee of GSK Biologicals.

V. Brichard: GSK employee.

All other authors have declared no conflicts of interest.