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Table 1 Clinical Trials of mRNA Encoding Immunostimulants

From: mRNA vaccine for cancer immunotherapy

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.