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DRUG:

mRNA-4157

i
Other names: mRNA-4157, mRNA 4157, V940, mRNA4157, V 940, V-940
Associations
Company:
Merck (MSD), Moderna
Drug class:
Immunostimulant
Related drugs:
Associations
22d
Enrollment open
|
Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • pemetrexed • mRNA-4157
24d
INTerpath-001: A Clinical Study of V940 Plus Pembrolizumab in People With High-Risk Melanoma (V940-001) (clinicaltrials.gov)
P3, N=1089, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
Enrollment closed
|
Keytruda (pembrolizumab) • mRNA-4157
1m
A Clinical Study of V940 Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005) (clinicaltrials.gov)
P1/2, N=230, Recruiting, Merck Sharp & Dohme LLC | Phase classification: P2 --> P1/2
Phase classification
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Keytruda (pembrolizumab) • Padcev (enfortumab vedotin-ejfv) • mRNA-4157
2ms
New P3 trial
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • pemetrexed • mRNA-4157
4ms
T Cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination With Pembrolizumab in the Phase 1 KEYNOTE-603 Study. (PubMed, Cancer Discov)
Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA INT approach in oncology.
P1 data • Journal • Combination therapy
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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Keytruda (pembrolizumab) • mRNA-4157
6ms
A Study of (Neo)Adjuvant V940 and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007) (clinicaltrials.gov)
P2/3, N=1012, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Apr 2029 --> May 2033
Trial completion date • Combination therapy • Metastases
|
Keytruda (pembrolizumab) • mRNA-4157
7ms
A Study of (Neo)Adjuvant V940 and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007) (clinicaltrials.gov)
P2/3, N=1012, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy • Metastases
|
Keytruda (pembrolizumab) • mRNA-4157
8ms
A Study of Adjuvant V940 and Pembrolizumab in Renal Cell Carcinoma (V940-004) (clinicaltrials.gov)
P2, N=272, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
Enrollment open
|
Keytruda (pembrolizumab) • mRNA-4157
8ms
Enrollment open
|
Keytruda (pembrolizumab) • mRNA-4157
8ms
New P2 trial
|
Keytruda (pembrolizumab) • mRNA-4157
8ms
New P2 trial
|
Keytruda (pembrolizumab) • mRNA-4157
9ms
New P2/3 trial • Combination therapy • Metastases
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Keytruda (pembrolizumab) • mRNA-4157
11ms
Enrollment open • Enrollment change
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
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EGFR mutation • ALK positive • ALK translocation • EGFR positive
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Keytruda (pembrolizumab) • mRNA-4157 • pembrolizumab subcutaneous (MK-3475 SC)
1year
Enrollment open
|
Keytruda (pembrolizumab) • mRNA-4157
1year
New P3 trial
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Keytruda (pembrolizumab) • mRNA-4157
over1year
mRNA-4157 (V940) individualized neoantigen therapy + pembrolizumab vs pembrolizumab in high-risk resected melanoma: Clinical efficacy and correlates of response (ESMO 2023)
There was a trend for enhanced efficacy of mRNA-4157 + pembro across BRAF V600E/K WT (n=96) (HR [95% CI]: 0.808 [0.366–1.784]) and MUT (n=61) subpopulations (0.332 [0.130–0.850]); however, considering ctDNA status by focusing on ctDNA-negative subpopulation increased similarity of efficacy across BRAF WT (n=68) and MUT (n=42) subgroups (0.334 [0.121–0.923] vs 0.069 [0.009–0.563]). Table: LBA49 ctDNA subgroup Patient criteria Molecular responders Patients with MRD at baseline that resolved during treatment (ctDNA positive at treatment initiation became ctDNA negative) OR Patients with no MRD at baseline that became ctDNA positive on treatment (MRec), and then ctDNA negative again Molecular non-responders Patients with MRD at baseline that did not resolve during treatment (ctDNA positive at treatment initiation and stayed positive) OR Patients with no MRD at baseline who showed molecular progression (MRec, ctDNA negative at treatment initiation became ctDNA positive and stayed positive) Conclusions These results suggest a potential relationship between ctDNA dynamics and treatment outcomes in pts with high-risk resectable melanoma and support further exploration in upcoming planned studies.
Late-breaking abstract • Clinical
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600K • BRAF wild-type
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RaDaR™ assay
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Keytruda (pembrolizumab) • mRNA-4157
over1year
New P3 trial
|
Keytruda (pembrolizumab) • mRNA-4157
over1year
mRNA Vaccine Slows Melanoma Recurrence. (PubMed, Cancer Discov)
Findings from the phase IIb KEYNOTE-942 trial indicate that the investigational vaccine mRNA-4157/V940 plus pembrolizumab is a potential adjuvant therapy for high-risk melanoma. Following surgery, patients who received the combination experienced a significant reduction in disease recurrence risk, compared with those given just PD-1 inhibitor.
Journal
|
Keytruda (pembrolizumab) • mRNA-4157
over1year
An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYNOTE-942) (clinicaltrials.gov)
P2, N=257, Recruiting, ModernaTX, Inc. | Active, not recruiting --> Recruiting | N=157 --> 257 | Trial completion date: Sep 2024 --> Sep 2029 | Trial primary completion date: Sep 2024 --> Sep 2029
Enrollment open • Enrollment change • Trial completion date • Trial primary completion date
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Keytruda (pembrolizumab) • mRNA-4157
over1year
Clinical • P2 data • PD(L)-1 Biomarker
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Keytruda (pembrolizumab) • mRNA-4157
over1year
Minimal residual disease by circulating tumor DNA as a biomarker of recurrence free survival in resected high-risk melanoma patients treated with mRNA-4157/V940, a personalized cancer vaccine, and pembrolizumab. (ASCO 2023)
MRD detection by plasma ctDNA assay at the start of adjuvant melanoma treatment is uncommon in mRNA4157-p201 but is associated with shorter RFS. Treatment with the combination of mRNA-4157/V940 and pembrolizumab was associated with prolonged RFS compared to pembrolizumab monotherapy in patients with high-risk resectable melanoma, irrespective of MRD status Additional analyses including assessment of longitudinal ctDNA patterns are ongoing. The association between MRD and mRNA-4157/V940 treatment effect will be further explored in upcoming planned studies.
Late-breaking abstract • Clinical • PD(L)-1 Biomarker • Minimal residual disease • Circulating tumor DNA
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RaDaR™ assay
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Keytruda (pembrolizumab) • mRNA-4157
over1year
mRNA-4157, a personalized cancer vaccine, in combination with pembrolizumab, demonstrates trend for improved recurrence free survival compared to pembrolizumab alone in adjuvant melanoma patients across tumor mutational burden subgroups (AACR 2023)
Our results indicate that mRNA-4157 demonstrates improvements in RFS irrespective of TMB status when administered in combination with pembrolizumab compared to pembrolizumab monotherapy in patients with resected high-risk cutaneous melanoma. The novel mechanism of action of mRNA-4157 may both deepen the activity of pembrolizumab and broaden the population of patients that can benefit from immune therapy. The association between TMB and mRNA-4157 treatment effect will be further explored in upcoming planned studies.
Combination therapy • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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PD-L1 expression • TMB-H • TMB-L
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FoundationOne® CDx
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Keytruda (pembrolizumab) • mRNA-4157
over1year
Enrollment closed • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
|
EGFR mutation • ALK positive • ALK translocation • EGFR positive
|
Keytruda (pembrolizumab) • mRNA-4157
2years
Trial completion date • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
|
EGFR mutation • ALK positive • ALK translocation • EGFR positive
|
Keytruda (pembrolizumab) • mRNA-4157
almost4years
Clinical • Enrollment change • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
|
EGFR mutation • ALK positive • ALK translocation
|
Keytruda (pembrolizumab) • mRNA-4157
over4years
[VIRTUAL] Bioinformatics algorithm of mRNA-4157 identifies neoantigens with pre-existing TIL reactivities in colorectal tumors (AACR-II 2020)
The bioinformatics algorithm for mRNA-4157 is able to predict and select neoantigens with pre-existing TIL reactivities based on human ex vivo assays for vaccine designs with high accuracy.
CD8 (cluster of differentiation 8)
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TILs
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mRNA-4157