intismeran autogene (mRNA-4157) / Merck (MSD), Moderna - LARVOL DELTA

INTerpath-007: A Study of (Neo)Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007) (clinicaltrials.gov) - P2/3 | N=46 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

A clinical study of V940 in people with non-small cell lung cancer (V940-013) (clinicaltrialsregister.eu) - P1/2 | N=15 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1/2 trial • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Personalized and HPV cancer vaccines in head and neck squamous cell carcinoma: from concept to clinical implementation. (PubMed, Transl Oncol) - "Compounds such as TG4050, mRNA-4157, and PGV001 have shown early, hypothesis-generating signals of activity (from small early-phase studies), particularly in the adjuvant setting. HPV-targeted vaccines, including PDS0101, BNT113, and CUE-101, are being explored in HPV-positive HNSCC, mainly in combination with ICIs...The greatest clinical potential of therapeutic vaccination may lie in earlier disease stages, where the tumor burden is lower and immune modulation more feasible. Further clinical and translational research is needed to define the optimal integration of vaccine-based therapies into multimodal treatment paradigms for HNSCC."

IO biomarker • Journal • Review • Head and Neck Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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) - P1 | "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."

Combination therapy • Journal • P1 data • Tumor-specific neoantigens • Cutaneous Melanoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8

KEYNOTE-603: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=161 | Active, not recruiting | Sponsor: ModernaTX, Inc. | N=242 ➔ 161 | Trial completion date: Aug 2027 ➔ Nov 2027 | Trial primary completion date: Aug 2027 ➔ Nov 2027

Enrollment change • Trial completion date • Trial primary completion date • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Computational identification of shared neoantigens from TP53, KRAS, and BRAF hotspot mutations for pan-cancer therapeutic vaccine development (ESMO-TAT 2026) - "The KRAS-derived peptides match sequences used in ongoing clinical trials (TG01, mRNA-4157)... We identified four shared neoantigen candidates with strong MHC-I binding derived from common oncogenic mutations. TP53 mutations occur in roughly half of all cancers, while KRAS mutations drive pancreatic, colorectal, and lung adenocarcinomas; T-cell reactivity testing of these peptides is the logical next step. This approach may facilitate development of off-the-shelf vaccines targeting recurrent driver mutations."

IO biomarker • Pan tumor • Tumor-specific neoantigens • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • TP53

Intismeran autogene (V940/mRNA-4157) plus bacillus Calmette-Guérin (BCG) versus BCG alone for high-risk non–muscle-invasive bladder cancer: The phase 2 INTerpath-011 study. (ASCO-GU 2026) - P2 | "Previously presented at ESMO Congress 2025, FPN: 3135eTiP, Petros Grivas et al. – Reused with permission."

P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Nanovaccines in Cancer Immunotherapy: Lymph Node-Targeted Strategies and Mechanistic Insights. (PubMed, Curr Pharm Des) - "Nanovaccine platforms can potentially overcome some constraints of conventional vaccines by enhancing lymph node targeting, antigen stability, and immunogenicity. Further research in this field could further advance targeted cancer immunotherapy."

Journal • Melanoma • Oncology • Solid Tumor • STING

Melanoma vaccines: current R&D landscape, translational hurdles, and future outlook-a perspective drawn from 442 clinical trials. (PubMed, Front Immunol) - "Most trials focused on Stage III/IV patients (91.1%): key trials showed mRNA-4157 + pembrolizumab reduced recurrence/death risk by 49% in resected melanoma, and herpes simplex virus RP1 + nivolumab achieved 58.3% objective response rate (ORR) in ICI-resistant patients. However, challenges include tumor heterogeneity, immunosuppressive tumor microenvironment (TME), inefficient delivery, geographical R&D imbalance, and low Phase III conversion. Interdisciplinary collaboration, international multicenter trials, optimized clinical design (e.g., early-stage patient enrollment), and policy support are needed to advance their clinical translation."

Journal • Review • Herpes Simplex • Melanoma • Oncology • Skin Cancer • Solid Tumor • CSF2 • IL2

A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005) (clinicaltrials.gov) - P1/2 | N=230 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Phase 1/2 INTerpath-005 study: V940 (mRNA-4157) plus pembrolizumab with or without enfortumab vedotin (EV) for resected high-risk muscle-invasive urothelial carcinoma (MIUC). (ASCO-GU 2025) - P1/2 | " Eligibility criteria for the perioperative cohort include age ≥18 years, diagnosis of MIBC (T2-T4aN0M0 or T1-T4aN1M0) with urothelial carcinoma histology, eligibility and willingness to undergo radical cystectomy (RC) + pelvic lymph node dissection (PLND), and cisplatin ineligibility. The primary end points are safety (perioperative cohort) and DFS per investigator assessment (adjuvant cohort). Secondary end points are pathologic complete response and pathologic downstaging (perioperative cohort); overall survival, distant metastasis–free survival per investigator, safety, and tolerability (adjuvant cohort)."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Personalized Cancer Vaccine Shows Durable Benefit at 5 Years. (PubMed, Cancer Discov) - "Five-year data from the phase IIb KEYNOTE-942 study show that the mRNA-based neoantigen vaccine intismeran autogene continues to reduce the risk of melanoma recurrence or death by roughly 49% when combined with pembrolizumab. This durability strengthens confidence in the personalized vaccine strategy, but a larger phase III trial will provide the decisive findings."

Journal • Melanoma • Oncology • Solid Tumor

Insights into RAS-driven melanoma and its therapeutic implications. (PubMed, Cancer Treat Rev) - "Ongoing combination strategies include MEK inhibition with type II RAF inhibitors (naporafenib plus trametinib in phase III trial), ERK1/2 or ERK5 inhibitors, PI3K/mTOR pathway blockade, or CDK4/6 inhibition. Additional investigational approaches include mutation-specific RAS inhibitors (G12C inhibitors already approved for other cancers), NRAS-specific or pan-RAS inhibitors (daraxonrasib in phase III trial for other cancers), targeted protein degradation, RAS-directed peptide and mRNA vaccines (mRNA-4157). NRAS Q61K-derived neoepitopes bound to HLA-A*01:01 have been recognized as immunogenic, suggesting that mutation-specific immunotherapies could represent a promising future strategy. In conclusion, the advent of promising and emerging therapies is set to transform the management of RAS-driven melanoma, making a personalized, biomarker-informed treatment strategy essential for optimizing patient outcomes."

IO biomarker • Journal • Review • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • Targeted Protein Degradation • KRAS • NRAS

Biomimetic and personalized nanovaccines in cancer immunotherapy: Design innovations, translational challenges, and future directions. (PubMed, J Adv Res) - "This review synthesizes recent advances in biomimetic and personalized nanovaccine design, highlighting clinical progress in lipid nanoparticle (LNP)-based vaccines such as BNT111 and mRNA-4157, emerging innate immune adjuvants including Toll-like receptor (TLR) and stimulator of interferon genes (STING) agonists, and rational combination strategies with immune checkpoint blockade. Key safety and quality consideration including immunotoxicity, off-target immune activation, and batch heterogeneity are critically evaluated alongside emerging engineering solutions. Finally, future directions integrating AI-guided neoantigen prediction, modular microfluidic manufacturing, and multi-omic biomarker frameworks are discussed to accelerate next generation cancer nanovaccine translation."

IO biomarker • Journal • Review • Oncology • STING

INTerpath-007: A phase II/III, adaptive, randomized study of neoadjuvant and adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) for treatment of resectable locally advanced (LA) cutaneous squamous cell carcinoma (cSCC) (ESMO 2024) - P2/3 | "The key secondary end points are pathological complete response assessed by blinded independent central review (BICR) and overall survival. Other secondary end points include ORR per RECIST v1.1 by investigator assessment, pathological partial response by BICR, disease-free survival by investigator assessment, and safety."

Clinical • Metastases • P2/3 data • Tumor mutational burden • Cutaneous Melanoma • Melanoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • TMB

Distant metastasis-free survival results from the randomized, phase 2 mRNA-4157-P201/KEYNOTE-942 trial. (ASCO 2023) - P2 | "mRNA-4157 in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma significantly prolonged DMFS compared to pembrolizumab. These results provide further evidence that a personalized neoantigen approach is potentially beneficial for cancer patients. A phase 3 randomized study will be initiated in patients with melanoma."

Clinical • Late-breaking abstract • P2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

INTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC). (ASCO-GU 2025) - P2 | "Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor

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."

Clinical • Combination therapy • IO biomarker • Tumor mutational burden • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • PD-L1 • TMB

INTerpath-004: A Phase 2, Randomized, Double-Blind Study of Pembrolizumab with V940 (mRNA-4157) or Placebo in the Adjuvant Treatment of Renal Cell Carcinoma (KCRS 2024) - P2 | "Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing."

Clinical • P2 data • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. (PubMed, Lancet) - P2 | "Adjuvant mRNA-4157 plus pembrolizumab prolonged recurrence-free survival versus pembrolizumab monotherapy in patients with resected high-risk melanoma and showed a manageable safety profile. These results provide evidence that an mRNA-based individualised neoantigen therapy might be beneficial in the adjuvant setting."

Journal • Monotherapy • P2b data • Tumor-specific neoantigens • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

A personalized cancer vaccine, mRNA-4157, combined with pembrolizumab versus pembrolizumab in patients with resected high-risk melanoma: Efficacy and safety results from the randomized, open-label Phase 2 mRNA-4157-P201/Keynote-942 trial (AACR 2023) - "mRNA-4157 in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma significantly prolonged RFS compared to pembrolizumab without an increase in clinically meaningful adverse events. These results are the first to demonstrate improvement of RFS over adjuvant standard of care PD-1 blockade in resected high-risk melanoma and provide the first randomized evidence that a personalized neoantigen approach is potentially beneficial for cancer patients. A phase 3 study will be initiated in patients with melanoma."

Clinical • IO biomarker • P2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

A phase 1, open-label, multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone and in combination in participants with solid tumors (SITC 2024) - "Background Neoantigens are tumor-specific non-synonymous mutations in proteins that are processed and presented in major histocompatibility complex molecules, driving anti-tumor T-cell responses.1 mRNA-4157 is a novel mRNA-based individualized neoantigen therapy that encodes up to 34 neoantigens mediating specific anti-tumor T-cell activation.2 In adjuvant melanoma, INT plus pembrolizumab induced durable improvements in RFS & DMFS.3 Neoantigens have been seen in less immune-infiltrated, high-recurrence tumors such as PDAC, gastric/GEJ and NSCLC, and long-term survivors demonstrate neoantigen specific T-cell responses.4 5 We hypothesize that mRNA-4157 will invigorate specific T-cells, potentially delaying recurrence and minimizing micro-metastases, thus affecting patient outcome.mRNA-4157-P101 is a single arm study to evaluate safety, tolerability, immunogenicity, ctDNA, anti-tumor efficacy and exploratory biomarkers of mRNA-4157 combination in solid tumors (figure..."

Clinical • P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 3 INTerpath-009 study: Individualized neoantigen therapy V940 (mRNA-4157) plus pembrolizumab for resected stage II-IIIB (N2) NSCLC with incomplete pathological response to neoadjuvant immunochemotherapy (AACR 2025) - P3 | "Secondary endpoints include OS, distant metastasis-free survival, DFS after next-line therapy, lung cancer-specific survival, patient-reported outcomes, and safety. The first pt was screened on October 21, 2024, and recruitment is ongoing."

Clinical • IO biomarker • P3 data • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

Individualized neoantigen therapy mRNA-4157 (V940) plus pembrolizumab in resected melanoma: 3-year update from the mRNA-4157-P201 (KEYNOTE-942) trial. (ASCO 2024) - P2 | "The current analysis with ∼3 y median follow-up showed durable and meaningful long-term RFS and DMFS benefit with mRNA-4157 + pembro vs pembro alone. A trend for improved OS with combo tx was also observed. HLA and translational subgroup results suggest mRNA-4157 + pembro may benefit a broader pt population vs pembro alone."

Clinical • IO biomarker • Late-breaking abstract • Tumor-specific neoantigens • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • PD-L1 • TMB

Intismeran autogene (mRNA-4157 or V940) (Merck (MSD) Press Release) - "The randomized Phase 2 study for adjuvant renal cell carcinoma is fully enrolled. Randomized Phase 2 studies for patients with resected muscle invasive and resected non-muscle invasive bladder cancer are enrolling, a Phase 2 study of first-line treatment for patients with metastatic melanoma and a Phase 2 study of first-line treatment for patients with metastatic squamous NSCLC are also enrolling."

Enrollment status • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Urothelial Cancer