TriMix-DC (ex-vivo autologous dendritic cells vaccine) / eTheRNA immunotherapies - LARVOL DELTA

Immune cell profiling of melanoma metastases from patients treated with TriMixDC-MEL dendritic cell therapy in combination with ipilimumab. (ASCO 2017) - P2; "Semi-automated analysis (Definiens software) was applied to estimate the tumor area stained for CD8, CD20, CD163, OX40, ICOS and LAG3, % of FOXP3 positive T-cells and IRF1-positive tumor nuclei. This study identified a set of potentially new predictive biomarkers, including virus response related genes, for DB following ipilimumab plus TriMixDC-MEL therapy. Further prospective validation is warranted."

Biomarker • Clinical • Combination therapy • Biosimilar • Melanoma

[VIRTUAL] Step by step optimization of mRNA-electroporated dendritic cells during a phase I / II vaccine trial in stage IV cutaneous melanoma patients: an increase in survival correlates with higher immunoscore in metastases, and upregulation of PEBP1 in peripheral blood (ADO 2020) - P1/2 | "Our data suggests optimal maturation stimulus and delivery route of DCs, and confirm early-on biomarkers we described earlier. This will help to maximize vaccine effects in upcoming trials against various cancers."

Clinical • Cutaneous Melanoma • Eosinophilia • Melanoma • Oncology • Solid Tumor • BIRC5 • CD40LG • CD70 • PEBP1 • TLR4

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. (PubMed, Cancer Immunol Immunother) - "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."

Clinical • IO Biomarker • Journal • P2 data • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CD40LG • CD70 • CD9 • CSF2 • PD-L1 • STAT2 • TLR4

Phase II study of autologous mRNA electroporated dendritic cells (TriMixDC-MEL) in combination with ipilimumab in patients with pretreated advanced melanoma. (ASCO 2014) - Presentation time: Monday, Jun 2; 1:15 PM - 4:15 PM; Abstract #3014; P2, N=39; NCT01302496; "The 6-mths DCR by irRC is 50% (95% CI 34-66). Median PFS and OS are respectively 6.2 (95% CI 3-9), and 14.4 mths (95%CI 10-18)."

P2 data • Melanoma • Oncology

eTheRNA completes enrolment of low dose cohort for phase 1b study of TriMix mRNA-based cancer specific immunotherapy (ECI-006) in melanoma (PRNewswire) - P1b, N=10; E011-MEL study (NCT03394937); Sponsor: eTheRNA immunotherapies; "A total of 44 doses have been administered with no adverse safety signals....Initial immunological data from the low dose cohort are expected in the second half of 2018....We will begin enrolment for the high dose cohort of this study during the second quarter of this year."

Enrollment closed • P1 data • Trial status • Melanoma • Oncology • Solid Tumor

eTheRNA enrols first patient in high dose cohort of phase 1b study of TriMix mRNA-based cancer specific immunotherapy (ECI-006) in melanoma (eTheRNA Press Release) - P1b, N=10; E011-MEL (NCT03394937); Sponsor: eTheRNA immunotherapies; "eTheRNA immunotherapies...announces that it has enrolled the first patient in the high dose cohort of its Phase 1b study (E011-MEL) of ECI-006 as an adjuvant therapy in metastatic melanoma patients...The high dose cohort (1800 µg) of the E011-MEL study aims to recruit ten patients, at centers in Belgium and Spain, who will receive five injections of ECI-006 administered intranodally over a period of 14 weeks....Results, including immunological responses and the full safety dataset, from both cohorts in the E011-MEL study are anticipated in the first half of 2019."

P1 data • Trial status • Melanoma • Oncology • Solid Tumor

TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma. (PubMed, J Immunother Cancer) - P2; "TriMixDC-MEL IPI treatment results in robust CD8+ T-cell responses in a meaningful portion of stage III or IV melanoma patients, and obviously in patients with a clinical response. The levels of polyfunctional and multiantigen T-cell responses measured in patients with a complete response, particularly in patients evidently cured after 5+ years of follow-up, may provide a benchmark for the level of immune stimulation needed to achieve a durable clinical remission."

Clinical • Journal • CD40LG • CD70 • Tyrosinase

Multiclonal T cell dendritic cell vaccine immune responses correlate with clinical response in TriMixDC-MEL IPI study, a study with TriMix/tumor antigen mRNA dendritic cells plus ipilimumab in patients with advanced melanoma (CIMT 2019) - "These strong and multi-antigen T-cell responses in CR patients that remain long term progression free may provide a clue to the level of immune awakening needed to achieve good clinical activity. Further research is needed to investigate the correlations between the mRNA expression levels of TAAs by the tumor versus T-cell and clinical responses towards the vaccine."

Clinical • IO Biomarker

A phase I/II vaccine clinical trial in metastatic malignant melanoma patients with step by step optimized mRNA-electroporated dendritic cells: an increase in survival correlates with eosinophilia and upregulation of PEBP1 (CIMT 2019) - "...The outcome of the described modifications resulted in a mean survival of 36.5 months in CD40L-DC-treated patients, while that of Trimix-DC-treated ones was 19 months...The insights from this trial point to the maturation stimulus and delivery route which achieve the best survival, and also support the usefulness of two ´early on´ biomarkers we described earlier. This information will be useful to maximize vaccine effects in upcoming trials against melanoma and other cancers."

Clinical • P1/2 data

A phase I/II vaccine clinical trial in metastatic malignant melanoma patients with step by step optimized mRNA-electroporated dendritic cells: an increase in survival correlates with eosinophilia and upregulation of PEBP1 (CIMT 2019) - "...The outcome of the described modifications resulted in a mean survival of 36.5 months in CD40L-DC-treated patients, while that of Trimix-DC-treated ones was 19 months...The insights from this trial point to the maturation stimulus and delivery route which achieve the best survival, and also support the usefulness of two ´early on´ biomarkers we described earlier. This information will be useful to maximize vaccine effects in upcoming trials against melanoma and other cancers."

Clinical • P1/2 data

Multiclonal T cell dendritic cell vaccine immune responses correlate with clinical response in TriMixDC-MEL IPI study, a study with TriMix/tumor antigen mRNA dendritic cells plus ipilimumab in patients with advanced melanoma (CIMT 2019) - "These strong and multi-antigen T-cell responses in CR patients that remain long term progression free may provide a clue to the level of immune awakening needed to achieve good clinical activity. Further research is needed to investigate the correlations between the mRNA expression levels of TAAs by the tumor versus T-cell and clinical responses towards the vaccine."

Clinical • IO Biomarker