A randomized controlled phase II clinical trial on mRNA electroporated autologous monocyte-derived dendritic cells (TriMixDC-MEL) as adjuvant treatment for stage III/IV melanoma patients who are disease-free following the resection of macrometastases.

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.

• Authors: Yanina Jansen, Vibeke Kruse, Jurgen Corthals, Kelly Schats, Pieter-Jan van Dam, Teofila Seremet, Carlo Heirman, Lieve Brochez, Mark Kockx, Kris Thielemans, Bart Neyns
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 69 Issue 12 Pg. 2589-2598 (Dec 2020) ISSN: 1432-0851 [Electronic] Germany
• PMID: 32591862 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

• CD27 Ligand
• CD70 protein, human
• RNA, Messenger
• TLR4 protein, human
• Toll-Like Receptor 4
• CD40 Ligand

Topics

• Adult
• Aged
• Aged, 80 and over
• CD27 Ligand (genetics, immunology)
• CD40 Ligand (genetics, immunology)
• Combined Modality Therapy (methods)
• Dendritic Cells (metabolism, transplantation)
• Disease-Free Survival
• Electroporation
• Female
• Follow-Up Studies
• Humans
• Immunotherapy (methods)
• Male
• Melanoma (immunology, mortality, secondary, therapy)
• Middle Aged
• Neoplasm Recurrence, Local (epidemiology, prevention & control)
• Neoplasm Staging
• RNA, Messenger (genetics, immunology)
• Skin Neoplasms (immunology, mortality, pathology, therapy)
• Surgical Procedures, Operative
• Toll-Like Receptor 4 (genetics, immunology)
• Transplantation, Autologous (methods)
• Young Adult