The DOI matches its Crossref record.
A phase I multicenter study to assess 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.
Abstract
2523 Background: T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses. Immunizing patients against such neoantigens in combination with a checkpoint inhibitor (CPI) may elicit greater anti-tumor responses than CPI alone. Mutations are rarely shared between patients, thus requiring a personalized approach to vaccine design. Methods: A phase I dose escalation study of mRNA-4157 as adjuvant monotherapy in patients with resected solid tumors (melanoma, bladder carcinoma, HPV negative HNSCC, NSCLC, SCLC, MSI-High, or TMB High cancers) and in combination with pembrolizumab in patients with advanced or metastatic cancer is being conducted to evaluate safety. mRNA-4157 is a lipid encapsulated personalized vaccine encoding multiple neoantigens selected using a proprietary algorithm designed to induce neoantigen specific T cells and associated anti-tumor responses. Patients may receive up to 9 cycles (Q3W) of mRNA-4157 by intramuscular injection (0.04 – 1 mg). In the combination arm, pembrolizumab (200 mg) is administered for two cycles prior to combination with mRNA-4157; patients may continue pembrolizumab after completion of 9 cycles of combination therapy. Primary end points include safety, tolerability, and recommended phase 2 dose. Results: 33 patients received mRNA-4157; 13 as monotherapy and 20 in combination with pembrolizumab. No DLTs were reported, and treatment related AEs have generally been of low grade and reversible, and no drug related SAEs or AEs ≥ grade 3 have been observed. Of the 13 patients on adjuvant monotherapy (3 melanoma, 8 NSCLC, 2 MSI-High), 12 patients remain disease free on study, median follow-up of 8 months. 20 patients have been treated in combination (1 TMB-high, 4 bladder, 2 HNSCC, 1 melanoma, 7 NSCLC, 2 SCLC, 3 MSI-high), 12 had progressed on prior CPI, 16 have been restaged and there are 1 CR (on pembrolizumab prior to vaccination), 2 PR, 5 SD for at least 5 combination cycles, 5 PD, 2 iuPD, and 1 patient is non-evaluable for response but remains on study. Neoantigen specific T cell responses have been detected by IFN-γ ELISpot from PBMCs. Conclusions: mRNA-4157 is safe and well tolerated at all dose levels tested. Clinical responses have been observed in combination with pembrolizumab and neoantigen-specific T cells have been induced, supporting the advancement of mRNA-4157 to phase 2. Clinical trial information: NCT03313778.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Finally, the overall response rate (ORR) for the treatment of 10 cases of HPV-negative head and neck squamous cell carcinoma (HPV-HNSCC) with the mRNA-4157 vaccine was 50%, of which 2 cases achieved complete remission (CR).355–358”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [358]
In the citing paper
“Finally, the overall response rate (ORR) for the treatment of 10 cases of HPV-negative head and neck squamous cell carcinoma (HPV-HNSCC) with the mRNA-4157 vaccine was 50%, of which 2 cases achieved complete remission (CR).355–358”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [356]
In the citing paper
“Moderna’s mRNA personalized cancer vaccine mRNA-4157 is comprised of 34 unique neoantigen genes (encoded by tumor-specific mutated genes) combined in a single mRNA vaccine; this vaccine was proven safe and tolerable in combination with pembrolizumab in phase I clinical trials.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [358]
In the citing paper
“Moderna’s mRNA personalized cancer vaccine mRNA-4157 is comprised of 34 unique neoantigen genes (encoded by tumor-specific mutated genes) combined in a single mRNA vaccine; this vaccine was proven safe and tolerable in combination with pembrolizumab in phase I clinical trials.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [356]
In the citing paper
“Several personalized cancer vaccines using lipid nanoparticle–mRNA formulations have also entered clinical trials210–212.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [211]
In the citing paper
“In the monotherapy group, 14 out of 16 patients remained disease-free during the study, with a median follow-up time of 8 months210,211.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [211]
In the citing paper
“In the combination group, the overall response rate in the cohort (human papillomavirus-negative, immune checkpoint inhibitor-naive, head and neck squamous cell carcinomas) was 50% and the median progression-free survival was 9.8 months210,211.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [211]
In the citing paper
“For example, mRNA-4157 is a personalized cancer vaccine encoding up to 34 neoantigens210,211.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [211]
Citations
Cited by
Sorted by citations
Items 101–144 of 144
Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery
Raza, A., Zhang, R., Lu, R., Wen, J., & Wu, W. (2025) · Nanomedicine · doi:10.1080/17435889.2025.2555507 · Cited by 7
Lipid nanoparticle-assisted mRNA therapy for cancer treatment
Kim, H.-J., Le, N. D., Oh, H.-J., Kim, B., Yoo, E., Kim, J., & Yim, H. (2025) · Applied Physics Reviews · doi:10.1063/5.0247029 · Cited by 5
Filippini, D. M., & Tourneau, C. L. (2026) · Translational Oncology · doi:10.1016/j.tranon.2026.102715 · Cited by 7
“These results could justify further evaluation of this vaccine combined with pembrolizumab in a randomized trial [22,23].”
Future prospects in mRNA vaccine development
Mbatha, L. S., Akinyelu, J., Maiyo, F., & Kudanga, T. (2023) · Biomedical Materials · doi:10.1088/1748-605x/aceceb · Cited by 7
“Results revealed that vaccination with mRNA4157monotherapy or a combined regimen ofmRNA4157 and Pembrolizumab was remarkably effective in eliciting neoantigen-specific T-cell responses alongside an acceptable safety profile [195].”
BackgroundShah, D., Shah, V., Shah, K., Shah, P. J., Alsadhan, M., Haslam, A., Prasad, V. K., Qazilbash, M. H., Chakraborty, R., & Mohyuddin, G. R. (2025) · EClinicalMedicine · doi:10.1016/j.eclinm.2025.103378 · Cited by 4
Unraveling the potential: mRNA therapeutics in oncology
Gawalski, K., Przybyszewska, W., Hunia, J., Gawalska, A., & Rymarz, A. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1643444 · Cited by 6
Azhdarifam, S., Metanat, M., Ghobeishavi, N., Nouroloyouni, S., & Jahanban‐Esfahlan, R. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119529 · Cited by 5
Advances, opportunities and challenges in developing therapeutic cancer vaccines
Duan, Z., Yang, D., Yuan, P., Dai, X., Chen, G., & Wu, D. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104198 · Cited by 4
Adoptive Cell Transfer and Vaccines in Melanoma: The Horizon Comes Into View
Warner, A. B., Sullivan, R. J., & Sarnaik, A. A. (2022) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_351114 · Cited by 5
Khushalani, N. I., Brohl, A. S., Markowitz, J., et al. (2020) · doi:10.1136/jitc-2020-sitc2020.0797 · Cited by 4
Chen, H., Zhang, J., Huang, J., Wu, Z., Tang, L., Tian, Y., Gao, S., Huang, S., Cao, J., Chen, J., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07470-7 · Cited by 3
“Patient-specific neoantigen-targeting vaccines represent a promising personalized therapeutic approaches to enhance the precision of T cell therapies, strengthen immune responses against unique tumor-specific antigens (TSAs), and counter tumor antigen heterogeneity [222–225].”
Heendeniya, S. N., Chen, S., Bhatti, S. H., Zahra, Q. U. A., Rahimizadeh, K., Poudel, B. H., Wilton, S. D., & Veedu, R. N. (2025) · Experimental Biology and Medicine · doi:10.3389/ebm.2025.10784 · Cited by 3
Choy, O. T., Fletcher, N. L., Huda, P., Bell, C. A., Owen, D. J., & Whittaker, A. K. (2026) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6c00045 · Cited by 6
mRNA therapy: a precise and efficient approach for disease treatment
Zhou, J., & Yang, Y. (2024) · Life Medicine · doi:10.1093/lifemedi/lnae035 · Cited by 3
“For example, mRNA-4157 was designed based on the unique mutational signature of patient’s tumor DNA sequence to create personalized vaccines, which can promote the generation of specific T-cell anti-tumor responses [5].”
Pioneering next-generation mRNA therapeutics through molecular engineering and delivery optimization
Qi, L., Li, Z., Feng, Z., Liu, J., & Chen, X. S. (2025) · Materials Today · doi:10.1016/j.mattod.2025.08.023 · Cited by 3
Mucosal and transdermal delivery strategies for mRNA: Transforming the clinical applications
Wang, L., & Deng, H. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114221 · Cited by 2
Carbon dot-lipidoid nanocarriers for superiorly biocompatible nasal mRNA cancer vaccination
Kim, H., Jeong, H., Kim, Y. A., Kim, K. S., Yun, J.-W., Li, F., Ling, D., & Na, K. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03844-7 · Cited by 3
“Recent studies have explored the use of LNPs in mRNA-based cancer vaccines, such as BioNTech’s BNT111 [8, 13] and Moderna’s mRNA-4157 [14, 15] designed to deliver personalized neoantigens for treating solid tumors.”
Fredericq, L., Hamouda, A. E. I., Zhong, Z., Ginderachter, J. A. V., Geest, B. G. D., & Laoui, D. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114799 · Cited by 3
Nanomedicine-Mediated Immunotherapy for Cancer Treatment
Hou, W., Song, W., Zhang, R., Lomova, M. V., Sadovnikov, А. V., & Song, Y. J. (2026) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5c02061 · Cited by 4
Bafleh, W. S., Abdulsamad, H. M. R., Al-Qaraghuli, S. M., Khatib, R. Y. E., Elbahrawi, R. T., Abdukadir, A. M., Alsawae, S. M., Dimassi, Z., Hamdan, H., & Kashir, J. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1198848 · Cited by 2
Liu, W., Su, H. L., Guo, P., Hong, L., Hao, X., & Li, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1537947 · Cited by 2
Protein Informatics and Vaccine Development: Cancer Case Study
Verma, S. K., Masand, N., Cheke, R. S., & Patil, V. M. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026623666221107160636 · Cited by 2
Neoantigen-based therapeutic cancer vaccine: Towards a bright future
Wang, Y., Zhao, G., Ma, P., Jiang, Y., Xing, S., Wang, S., & Li, N. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.107024 · Cited by 1
Cancer Vaccines: Another Aspect to Immunotherapy
Al-Janabi, I. I. (2024) · Al-Rafidain Journal of Medical Sciences · doi:10.54133/ajms.v7i1.1057 · Cited by 2
Bismuth based nanomaterials: Design, synthesis and applications in tumor synergistic therapy
Zhang, Q., Tu, J., Jiang, Y., Wang, H., Xue, W., Dong, C., Ouyang, R., & Miao, Y. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.114992 · Cited by 1
Gillman, L., Suleski, D., Graham, M. E., Ginn, S. L., & Hassan, M. M. (2026) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.6c00618 · Cited by 2
Meisel, A., & Pascolo, S. (2021) · healthbook TIMES Oncology Hematology · doi:10.36000/hbt.oh.2021.09.045 · Cited by 2
Roerden, M., & Walz, J. S. (2021) · best practice onkologie · doi:10.1007/s11654-021-00356-2
Roerden, M., & Walz, J. S. (2021) · Der Onkologe · doi:10.1007/s00761-021-01012-8
Messenger RNA Nanovaccine in Cancer Immunotherapy
Li, M., & Zhang, H. (2022) · Springer eBooks · doi:10.1007/978-3-031-17831-3_9
Personalized Cancer Vaccines Targeting Neoantigens
Himuro, H., & Sasada, T. (2022) · Springer eBooks · doi:10.1007/978-3-030-80962-1_291-1
Berzofsky, J. A., Olkhanud, P. B., & Maeng, H. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-79058-1.00014-1
The Application of mRNA in Treating Cancer
Wang, Y. (2023) · MedScien · doi:10.61173/whehp021
Azagury, A., Kaeek, M., Khoury, L. R., & Kost, J. (2023) · Wiley eBooks · doi:10.1002/0471238961.0418210717210104.a01.pub3
mRNA vaccines as a revolutionary approach to combat cancer
Mainali, N., Shrestha, A. B., Shrestha, S., Chapagain, S., Khanal, B., Shrestha, L. B., Shrestha, S., & Jaiswal, V. (2023) · Postgraduate Medical Journal · doi:10.1093/postmj/qgad138
mRNA vaccines: The new frontier
Yan, Z., Yang, M. J., Tian, E., & Lai, C. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19170-1.00021-8
Theodosis‐Nobelos, P., Kitiri, E. N., Christou, M., Pantelidou, M., & Rikkou‐Kalourkoti, M. (2025) · Pharmaceutical Nanotechnology · doi:10.2174/0122117385350610250112112855
Advanced Technologies for Cancer Immunotherapy: Focus on Gastrointestinal Cancers
Ahangarzadeh, S., Mohammadi, E., Yaghoobi, H., Shahzamani, K., Bahrami, A. A., Arezumand, R., Beikmohammadi, L., & Alibakhshi, A. (2025) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/0118715206369319250402150638
Personalized Cancer Vaccines Targeting Neoantigens
Himuro, H., & Sasada, T. (2025) · Springer eBooks · doi:10.1007/978-3-032-00773-5_291
Current perspectives of nanovaccines and nanomedicines in cancer treatment
Butt, A., Noor, A., & Din, F. U. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44579-8.00010-2
Head and neck cancer therapeutic vaccines: a review
Huetteman, A., & Rabinowits, G. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1773594
“These promising results need to be con-fi rmed in a randomized trial (69, 70).”
Raja, H. A., Malik, F., Fatima, H., & Babar, M. M. (2026) · Springer eBooks · doi:10.1007/978-981-95-3957-4_25
Cancer vaccines: comprehensive review
Clifford, R. E., Manu, N., Yang, Q., Arif, Z., Aggen, D. H., Bryan, M. E., Gupta, A., Shaw, H. M., Church, D., Corrie, P. G., et al. (2026) · BJS Open · doi:10.1093/bjsopen/zrag041
“In the combination cohort, pembrolizumab was initiated two cycles before the introduction of mRNA-4157, which was given intramuscularly every 3 weeks for up to nine cycles 53 .”
Vaccines as treatment for melanoma: an update review
Zhang, J., Cao, Q., Cen, Y., Zhang, L., & Chen, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1724490 · Cited by 1
“The neoantigens for the vaccine are identi fi ed via a proprietary algo-rithm, the construct had previously shown a favorable safety pro fi le and the capacity to elicit robust T-cell responses in preclinical models (104, 105).”
Metadata
- Authors
- Burris, H. A., Patel, M. R., Cho, D. C., Clarke, J. M., Gutierrez, M., Zaks, T. Z., Frederick, J., Hopson, K., Mody, K., Binanti-Berube, A., Robert-Tissot, C., Goldstein, B., Breton, B., Sun, J., Zhong, S., Pruitt, S. K., Keating, K., Meehan, R. S., & Gainor, J. F.
- Affiliations
- Sarah Cannon (US)
- Florida Cancer Specialists, Sarasota, FL;
- New York University (US)
- Duke Medical Center (US)
- Hackensack University Medical Center (US)
- Moderna Therapeutics (United States) (US)
- Moderna Tx, Cambridge, MA;
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2019-05-20
- Volume
- 37
- Issue
- 15_suppl
- Pages
- 2523-2523
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2947382141
- Cited by
- 144
- References
- 0
- Citations by year
- 2026: 13 · 2025: 31 · 2024: 18 · 2023: 31 · 2022: 22 · 2021: 18 · 2020: 11
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- personalized cancer vaccines, neoantigens, pembrolizumab, immune checkpoint inhibitors, solid tumors, adjuvant therapy, safety and tolerability, immunogenicity, tumor mutational burden, microsatellite instability, non-small cell lung cancer, melanoma, bladder cancer, head and neck squamous cell carcinoma, small cell lung cancer, dose escalation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
