A Phase I Study (E011-Mel) Of A Trimix-Based Mrna Immunotherapy (Eci-006) In Resected Melanoma Patients: Analysis Of Safety And Immunogenicity.

2641 Background: ECI-006 is a combination of TriMix (mRNAs encoding for dendritic cell [DC] activating molecules [CD40L, CD70 and caTLR4]), and mRNAs encoding for melanoma-specific tumor-associated antigens (TAAs): tyrosinase, gp100, MAGE-A3, MAGE-C2, and PRAME. DCs transfected ex vivo with TriMix and TAAs mRNAs showed significant clinical activity in combination with ipilimumab in metastatic melanoma without increasing toxicity. This study aims to assess the safety and immunogenicity of ECI-006 vaccine administered intranodally (i.n.) in an adjuvant setting for patients with resected melanoma. Methods: Twenty patients who underwent resection of stage IIc/III/IV cutaneous melanoma received 5 administrations of ECI-006 (either 600 µg or 1800 µg [n = 10, each]) injected i.n. on Day 1 and after 2, 4, 6 and 14 weeks. Treatment-emergent adverse events (TEAEs) were graded using CTCAE version 4.0.3. Blood samples for immune monitoring (ELISPOT and intracellular cytokine staining [ICS]) were collected pre-dose and at weeks 4, 7, 14 and 15. Results: Nineteen patients completed the treatment. One patient in the low dose group discontinued the study after 4 doses due to disease relapse. Administration of ECI-006 was well tolerated. No serious adverse events or TEAEs Grade 3 or higher were reported. Of all TEAEs, myalgia and fatigue were the most reported in 3 (15%) and 5 (25%) patients, respectively. ELISPOT and ICS were performed on T cells pre-stimulated in vitro for 10-12 days, using a previously in-house validated protocol. Vaccine-induced immune responses according to predefined criteria were detected in 4/10 and 3/9 patients treated with the low and high dose, respectively. Samples from these patients are currently being subjected to T-cell receptor repertoire analysis. Conclusions: Among patients undergoing resection of stage IIc/III/IV melanoma, i.n. administration of ECI-006 at 600 or 1800 µg was generally well tolerated. ECI-006 demonstrated to be immunogenic in a proportion of patients. These results warrant further development of ECI-006 in combination with anti-PD-1 therapy in melanoma patients. Clinical trial information: NCT03394937.