Table 1 Clinical Trials of mRNA Encoding Immunostimulants
NCT Number | Status | Phases | Disease | mRNA and Interventions | Formulation Type | Route | Combo | Sponsor (s) | Study Results |
|---|---|---|---|---|---|---|---|---|---|
NCT03788083 | Recruiting | Phase 1 | Early-stage Breast Cancer | Trimix mRNA (mRNA encoding CD40L, CD70, acTLR4) | Synthetic naked mRNA | Intratumoral | NA | Universitair Ziekenhuis Brusse, eTheRNA immunotherapies | Not available |
NCT03394937 | Recruiting | Phase 1 | Melanoma (resected) | ECI-006: a. Trimix mRNA, b. mRNA encoding TAAs: tyrosinase, gp100, MAGE-A3, MAGE-C2, PRAME | Synthetic naked mRNA | Intranodal | Trimix mRNA + TAA | eTheRNA immunotherapies | ECI-006 is well tolerated. Vaccine-induced immune responses were detected in 4/10 and 3/9 patients treated with low (600 μg) and high dose (1800 μg). ECI-006 shown immunogenic in a portion of patients. |
NCT01066390 | Completed | Phase 1 | Stage III/IV Malignant Melanoma (Previously treated, unresectable) | TriMixDC-MEL a. DC electroporated with TriMix mRNAs, b. TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | DC-based | Autologous DC treatment (i.v. and i.d.) | Trimix mRNA + TAA | Universitair Ziekenhuis Brussel | Immunotherapy with TriMixDC-MEL is safe and immunogenic. Antitumor activity with durable disease control is observed. Antigen-specific CD8+T-cells were detected in the blood of 4 of 5 patients. |
NCT01676779 | Completed | Phase 2 | Melanoma (disease free following macrometastases) | TriMixDC-MEL a. DC electroporated with TriMix mRNAs b. TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | DC-based | Autologous DC treatment (i.v. and i.d.) | Trimix mRNA + TAA | Universitair Ziekenhuis Brussel | TriMixDC-MEL is tolerable (symptom: transient local skin reactions, flu-like symptom, post-infusion chills), and may improve the 1-year disease-free survival rate (71% disease free in treatment group vs 35% in control arm). |
NCT01302496 | Completed | Phase 2 | Stage III/IV Malignant Melanoma (Previously treated, unresectable) | TriMixDC-MEL and i.v. CTLA-4 inhibitor ipilimumab | DC-based | Autologous dc therapeutics (i.v. and i.d.) | Trimix mRNA + TAA + Checkpoint inhibitor | Bart Neyns|Vrije Universiteit Brussel|Universitair Ziekenhuis Brussel | T-cell stimulation were shown in 12/15 patients. Immune responses were stronger in patients with complete or partial response. Multifunctional CD8+ T-cell responses were detected either elicited by TriMixDC-MEL IPI or on subsequent pembrolizumab treatment, may provide a benchmark for the level of immune stimulation needed to achieve a durable clinical remission. |
NCT03323398 | Recruiting | Phase 1/2 | Relapsed/ Refractory Solid Tumor Malignancies or Lymphoma | mRNA-2416 (mRNA encoding OX40L), alone (Phase I) or in combination with i.v. PD-L1 inhibitor, Durvalumab (Phase 2) | LNP | Intratumoral | mRNA LNP + Checkpoint inhibitor | ModernaTX, Inc. | Intratumoral mRNA-2416 is tolerable at all dose levels when dosed alone. Analyses of tumor post-treatment demonstrate increased OX40L protein expression, elevated PD-L1 levels and pro-inflammatory activity. |
NCT03739931 | Recruiting | Phase 1 | Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or LymphomaDose Expansion: Other solid tumors | mRNA-2752 (mRNA encoding OX40L, IL-23, IL-36Ƴ), alone (Phase I) or in combination with i.v. PD-L1 inhibitor, Durvalumab (Durva, Phase II) | LNP | Intratumoral | mRNA LNP + Checkpoint inhibitor | ModernaTX, Inc., AstraZeneca | Intratumoral mRNA-2752 given as monotherapy and in combination with PD-L1 inhibitor is tolerable at all dose levels studied, and administration can be associated with tumor shrinkage (52% Tumor reduction, 0.5 mg mRNA-2752 with durva in bladder carcinoma). Elevated IFN-γ, TNF-α, and PD-L1 levels were detected. |