Yanina Jansen1, Vibeke Kruse2, Jurgen Corthals3, Kelly Schats4, Pieter-Jan van Dam4, Teofila Seremet5, Carlo Heirman3, Lieve Brochez2, Mark Kockx4, Kris Thielemans3, Bart Neyns5. 1. Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium. Yanina.jansen@uzbrussel.be. 2. Department of Medical Oncology, Universitair Ziekenhuis Gent (UZ Gent), Ghent, Belgium. 3. Laboratory of Molecular and Cellular Therapy and Dendritic Cell-bank, Vrije Universiteit Brussel, Brussels, Belgium. 4. Histogenex NV, Antwerp, Belgium. 5. Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium.
Abstract
BACKGROUND: Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanoma patients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanoma patients. MATERIALS AND METHODS:Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). "Cross-over" was allowed at the time of non-salvageable recurrence. The primary endpoint was the percentage of patients alive and disease-free at 1-year. For a subset of patients, (formalin-fixed paraffin-embedded), tumor tissue samples were available for mRNA expression profiling and PD-L1 immunohistochemical staining. RESULTS: Baseline characteristics were well balanced. One-year after randomization, 71% of patients in the study arm were alive and free of disease compared to 35% in the control arm. After a median follow-up of 53 months (range 3-67), 23 patients experienced a non-salvageable melanoma recurrence (TriMixDC-Mel arm n = 9 and control arm n = 14).The median time to non-salvageable recurrence was superior in the TriMixDC-MEL arm (median 8 months (range 1-6) vs. not reached; log-rank p 0.044). TriMixDC-MEL-related adverse events (AE) consisted of transient local skin reactions, flu-like symptoms and post-infusion chills. No grade ≥ 3 AE's occurred. The mRNA expression profiling revealed four genes (STAT2, TPSAB1, CD9 and CSF2) as potential predictive biomarkers. CONCLUSION:TriMixDC-MEL id/iv as adjuvant therapy is tolerable and may improve the 1-year disease-free survival rate. Combination of optimized autologous monocyte-derived DC-formulations warrants further investigation in combination with currently approved adjuvant therapy options.
RCT Entities:
BACKGROUND: Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanomapatients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanomapatients. MATERIALS AND METHODS: Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). "Cross-over" was allowed at the time of non-salvageable recurrence. The primary endpoint was the percentage of patients alive and disease-free at 1-year. For a subset of patients, (formalin-fixed paraffin-embedded), tumor tissue samples were available for mRNA expression profiling and PD-L1 immunohistochemical staining. RESULTS: Baseline characteristics were well balanced. One-year after randomization, 71% of patients in the study arm were alive and free of disease compared to 35% in the control arm. After a median follow-up of 53 months (range 3-67), 23 patients experienced a non-salvageable melanoma recurrence (TriMixDC-Mel arm n = 9 and control arm n = 14).The median time to non-salvageable recurrence was superior in the TriMixDC-MEL arm (median 8 months (range 1-6) vs. not reached; log-rank p 0.044). TriMixDC-MEL-related adverse events (AE) consisted of transient local skin reactions, flu-like symptoms and post-infusion chills. No grade ≥ 3 AE's occurred. The mRNA expression profiling revealed four genes (STAT2, TPSAB1, CD9 and CSF2) as potential predictive biomarkers. CONCLUSION:TriMixDC-MEL id/iv as adjuvant therapy is tolerable and may improve the 1-year disease-free survival rate. Combination of optimized autologous monocyte-derived DC-formulations warrants further investigation in combination with currently approved adjuvant therapy options.
Authors: Raquel S Laureano; Jenny Sprooten; Isaure Vanmeerbeerk; Daniel M Borras; Jannes Govaerts; Stefan Naulaerts; Zwi N Berneman; Benoit Beuselinck; Kalijn F Bol; Jannie Borst; An Coosemans; Angeliki Datsi; Jitka Fučíková; Lisa Kinget; Bart Neyns; Gerty Schreibelt; Evelien Smits; Rüdiger V Sorg; Radek Spisek; Kris Thielemans; Sandra Tuyaerts; Steven De Vleeschouwer; I Jolanda M de Vries; Yanling Xiao; Abhishek D Garg Journal: Oncoimmunology Date: 2022-07-04 Impact factor: 7.723
Authors: Paolo A Ascierto; Christian Blank; Reinhard Dummer; Marc S Ernstoff; Soldano Ferrone; Bernard A Fox; Thomas F Gajewski; Claus Garbe; Patrick Hwu; Pawel Kalinski; Michelle Krogsgaard; Roger S Lo; Jason J Luke; Bart Neyns; Michael A Postow; Sergio A Quezada; Michele W L Teng; Giorgio Trinchieri; Alessandro Testori; Corrado Caracò; Iman Osman; Igor Puzanov; Magdalena Thurin Journal: J Transl Med Date: 2021-06-30 Impact factor: 5.531