Clinical advances and ongoing studies of mRNA vaccines for cancer treatment

Naked NCT02035956 1 An individualized tumor mutation signature with 10 selected neoepitopes for each patient. Melanoma (Stage III and IV) 13 none T cell responses against numerous vaccine neoepitopes One patient had CR and one patient had PR during vaccination treatment

NCT03394937 1 CD40L, CD70, caTLR4. TAAs: tyrosinase, gp100, MAGE-A3, MAGE-C2 and PRAME. Resected melanoma (stages IIc, III and IV) 20 none Vaccine-induced immune responses in four out of ten patients (low dose) and three out of nine patients (high dose) N / A

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• Arance Fernández AM
• Baurain JF
• Vulsteke C
• et al.

A phase I study (E011-MEL) of TriMix-based mRNA immunotherapy (ECI-006) in resected melanoma patients: analysis of safety and immunogenicity.

Protamine Formulation NCT01817738 1/2 PSA, PSMA, PSCA, STEAP1, PAP and MUC1. mCRPC 197 none N / A No significant differences in PFS

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• Stenz A
• Feyerabend S
• Syndic I
• et al.

Results of the Phase I/IIB, randomized, placebo-controlled study of CV9104, an mRNA-based cancer immunotherapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).

NCT00923312 1/2 MAGE-C1, MAGE-C2, NY-ESO-1, Survivin and 5T4 NSCLC (stages IIIb and IV) 46 none T cell responses against at least one TAA in 63% of patients No objective answers. PFS and OS not improved

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• Sebastian M
• Schroeder A
• Scheil B
• et al.

A phase I/IIa study of mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.

NCT01915524 1 MAGE-C1, MAGE-C2, NY-ESO-1, Survivin, 5T4 and MUC-1 NSCLC (Stage IV) 26 Local irradiation with or without pemetrexed, with or without EGFR-TKI Demonstrable antigen-specific immunity in 84% of patients One patient had PR in combination with chemotherapy and 46% had SD

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• Papachristofilou A
• hip MM
• Klinkhardt U
• et al.

Phase Ib evaluation of a self-adjuvanted protamine-formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer.

LPX formulation NCT02410733 1 NY-ESO-1, tyrosinase, MAGE-A3, TPTE melanoma 25 (monotherapy) 17 (combination) With or without standard PD-1 therapy Immune response to at least one TAA in over 75% of patients mRNA vaccine with anti-PD-1 therapy: six patients had PR and two had SD. mRNA vaccine monotherapy: Three patients had PR and seven had SD

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• Sahin U
• Um P
• Derhovanesian E
• et al.

An RNA vaccine boosts immunity in melanoma treated with checkpoint inhibitors.

NCT04503278 1/2 CLDN6 (CARVac) Solid tumors (CLDN6 CAR-T cells with CARVac) 7 CLDN6 CAR-T cells CAR-T cell transplantation in all patients Four patients had PR and one patient SD at the 6-week evaluation

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• Mackensen A
• Koenecke C
• Hanen J
• et al.

BNT211: a phase I/II study to evaluate the safety and efficacy of CLDN6 CAR T cells and vaccine-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumors.

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• Hanen J
• Gunther J
• Orleans NEW
• et al.

BNT211: a phase I study to evaluate the safety and efficacy of CLDN6 CAR T cells and CARVac-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumors.

LNP formulation NCT03480152 1/2 Neoantigen-specific mRNA Gastrointestinal Cancer 4 none Mutation-specific CD4+ and CD8+ T cell responses against predicted neoepitopes in three of four patients No objective clinical responses

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• cafri g
• Gartner JJ
• Zaks T
• et al.

mRNA vaccine-induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer.

NCT03313778 1 PCV encoding multiple neoantigens Solid tumors (resected) 13 (monotherapy) 19 (combination) pembrolizumab Detectable neoantigen T cell responses Vaccine monotherapy: 12 patients were cancer-free during study treatment with a median follow-up of 8 months. Combination treatment: One patient had CR prior to vaccination, two patients had PR, five patients had SD, five had PD, and two had unconfirmed PD

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• Burri’s HA
• Patel MR
• Cho DC
• et al.

A phase I multicenter study to evaluate the safety, tolerability and immunogenicity of mRNA-4157 alone in patients with resected solid tumors and in combination with pembrolizumab in patients with unresectable solid tumors.