Table 1.

Summary of the recent clinical trial data with mRNA melanoma vaccines/immunotherapies.

Target/Administration	Clinical Trial Number	Phase	Adjuvant therapy	Adverse event profile	Efficacy Profile	Reference
BNT111 (NY-ESO-1, MAGE-C3, Tyrosinase and TPTE), given I.V.	NCT02410733	I	With or without Cemiplimab	Flu-like symptom, no dose-limiting toxicity	Expansion and activation of circulating tumor-antigen-specific T cells with memory-function and strong cytotoxic activity	(51)
	NCT04526899	II			Monotherapy: 3/25 partial response, 7/25 stable disease, 1/25 complete metabolic remission; Combined with CPI: 6/17 with partial response
BNT122 (20 tumor-associated neo-antigens against melanoma), given I.V.	NCT03815058	I	With or without Atezolizumab	1/16 with Grade III fever/hypertension, no other Grade III or higher AE reported	De-novo neoantigen-specific T cell response in half (8/16) of patients, those with T-cell response had significantly longer progression-free survival than those without	(52)
BNT122 (20 tumor-associated neo-antigens against PDAC), given I.V.	NCT04161755	I
mRNA-4157 (multiple tumor-associated neo-antigens against solid malignancy), given I.M.	NCT03313778	I	With or without pembrolizumab	No Grade III or higher AE reported; no dose-limiting toxicity observed	Neoantigen specific T cell responses have been detected by IFN-γ ELISpot from PBMCs.	(53)
mRNA-4157 (multiple tumor-associated neo-antigens against melanoma), given I.M.	NCT03897881	II	With pembrolizumab	Serious treatment-related adverse events occurred in 14.4% of patients who received the combination arm of mRNA-4157/V940 and KEYTRUDA versus 10% with KEYTRUDA alone	Adjuvant treatment of mRNA-4157 in combination with pembrolizumab reduced the risk of recurrence or death in patients with metastatic melanoma by 44% (HR=0.56 [95% CI, 0.31-1.08]) as compared to patients receiving pembrolizumab alone	(54)
CV8102 (non-coding, non-capped RNA), given intratumorally	NCT03291002	I	With or without anti-PD-1 antibodies	Most frequent AEs were Grade 1/2, including fatigue, fever, chills, and headache	Increased intra-tumoral T cell infiltration in 4/8 patients receiving CV8102 alone, and 10/18 patients receiving CV8102, and anti-PD-1 therapy	(55)
mRNA-2752 (three cytokines OX40L/IL23/IL36γ), given intratumorally in patients with lymphoma and solid tumors including melanoma	NCT03739931	I	With or without durvalumab	Dose-limiting toxicity (due to cytokine release syndrome) in one of thirty patients receiving 8 mg	Increased IFNγ and TNFα expression in both tumor and plasma; Partial responses in 2/45 patients (DLBCL and squamous-cell bladder carcinoma); 15/45 patients with stable disease	(56)