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

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

Adjuvant intismeran autogene plus FOLFIRINOX in resectable pancreatic ductal adenocarcinoma: results from a phase I study (ESMO 2026) - No abstract available

Clinical • P1 data • Oncology • Pancreatic Ductal Adenocarcinoma

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

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

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

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

Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study. (PubMed, J Clin Oncol) - P2 | "Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After 5 years' follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma."

Journal • P2b data • Cutaneous Melanoma • Melanoma • Oncology • 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

Study Designs for INTerpath-002 and INTerpath-009 of Adjuvant Intismeran Autogene Plus Pembrolizumab for Non-Small Cell Lung Cancer. (PubMed, Ann Thorac Surg Short Rep) - "Recruitment is ongoing for both studies. Results from these studies will provide insight into the potential role of INT in NSCLC."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • 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

Translational Challenges and Opportunities in mRNA Cancer Vaccines. (PubMed, Cancer Discov) - "Messenger RNA (mRNA) cancer vaccines have progressed rapidly, with personalized platforms such as mRNA-4157 and BNT122 demonstrating feasibility, safety, and durable immune activity but limited scalability. Off-the-shelf constructs, including BNT111 and BNT113, enable faster, broader deployment, yet they risk reduced precision or immune tolerance...This mini-review synthesizes emerging clinical evidence and outlines strategies such as modular vaccine design, prime-boost vaccination regimens, and adaptive trial frameworks to reconcile these trade-offs and advance scalable, durable mRNA vaccines for broad oncologic impact. By dissecting the competing design pressures that shape mRNA vaccine performance, this mini-review proposes integrative strategies, spanning modular architectures, prime-boost regimens, and adaptive trials, to reconcile immunologic potency with manufacturability and safety, charting a roadmap toward next-generation cancer vaccines."

Journal • Review • Oncology

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

INTerpath-014: A Phase 3 Study of Adjuvant Intismeran Autogene (Intismeran) Plus Subcutaneous Pembrolizumab (Pembro SC) or Intismeran Monotherapy vs Placebo in Completely Resected High-Risk Stage I NSCLC (ESMO 2026) - No abstract available

Clinical • Monotherapy • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Individualized neoantigen therapy intismeran autogene (intismeran) plus pembrolizumab (pembro) in resected melanoma: 5-year update of the KEYNOTE-942 study. (ASCO 2026) - P2, P3 | "After a median 5 y of follow-up, intismeran + pembro continued to prolong RFS and DMFS, along with a trend for improved OS vs pembro alone in pts with high-risk resected melanoma. These long-term findings show that intismeran + pembro treatment benefits were sustained and durable over time, despite all pts having completed study treatment before primary analysis (2021). As reported previously, intismeran was well tolerated, with a manageable safety profile for intismeran + pembro."

Clinical • Tumor-specific neoantigens • Cutaneous Melanoma • Melanoma • Solid Tumor

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

INTerpath-013: A phase 2, randomized, double-blind study of intismeran autogene plus pembrolizumab and chemotherapy as first-line treatment for metastatic squamous non–small cell lung cancer. (ASCO 2026) - P2 | "Approximately 180 participants will be randomized 2:1 to receive 1 treatment cycle comprising intravenous pembrolizumab 400 mg Q6W (1 dose) plus carboplatin AUC 6 mg/mL/min Q3W (2 doses), with either paclitaxel 200 mg/m2 Q3W (2 doses) or nab-paclitaxel 100 mg/m2 QW (6 doses)...Any participant with PD at the 6-week scan will have treatment unblinded and those in arm A may receive exploratory treatment with up to 9 doses of intismeran plus docetaxel 75 mg/m2 Q3W until PD, unacceptable toxicity, or participant/physician decision; those in arm B will not receive further investigational treatment...Secondary endpoints include ORR and duration of response per RECIST v1.1 by BICR and safety. Enrollment began in December 2025 and is ongoing across 55 global sites."

Clinical • IO biomarker • Metastases • P2 data • CNS Disorders • Infectious Disease • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Merck and Moderna Announce Phase 3 INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA Met Endpoints of Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS) in Patients With Completely Resected Stage IIB-IV Melanoma (Businesswire) - "The trial met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival...At a pre-specified interim analysis, intismeran in combination with KEYTRUDA as adjuvant therapy demonstrated statistically significant and clinically meaningful improvements in RFS and DMFS compared to KEYTRUDA alone for patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma who had not undergone prior treatment with systemic therapy. In accordance with the trial protocol, the study will continue in order to evaluate other key secondary endpoints, including overall survival...These data will be presented at an upcoming international medical meeting and shared with regulatory authorities."

P3 data: top line • Melanoma

Personalized cancer vaccines: bridging immune-oncology and precision medicine for advanced therapeutics. (PubMed, Signal Transduct Target Ther) - "Despite advancements in therapeutic cancer vaccines, clinical translation has been hindered by limited efficacy, with Sipuleucel-T remaining the only FDA-approved therapeutic cancer vaccine to date. However, recent advances in personalized mRNA vaccines, such as Moderna's mRNA-4157 and BioNTech's autogene cevumeran, have demonstrated significant reductions in recurrence risk and improved survival across several cancer types, renewing optimism in the field...Increasing clinical evidence, especially in melanoma and pancreatic cancer, underscores the potential of these strategies to induce long-term protection and reduce recurrence. Overall, next-generation personalized cancer vaccines are advancing the transition from reactive treatment to proactive, precision-controlled cancer immunotherapy."

Journal • Review • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor

A clinical trial of V940 with or without MK-3475A in people with non-small cell lung cancer (V940-014) (clinicaltrialsregister.eu) - P2/3 | N=137 | Recruiting | Sponsor: Merck Sharp & Dohme LLC

Monotherapy • New P2/3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Intismeran autogene to induce de novo neoantigen-specific T cells as adjuvant therapy in melanoma. (ASCO 2026) - P2 | "Funded by This research was supported by Moderna, Inc., Cambridge, MA, USA, in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Clinical Trial Registration Number: NCT3313778 & NCT03897881 Background: Intismeran autogene (intismeran) is an individualized mRNA-based neoantigen (neoAg) therapy designed to enhance endogenous antitumor T-cell responses by targeting patient-specific tumor mutations. Complementary sequencing and functional analyses demonstrated that adjuvant therapy with intismeran plus pembro induced durable, polyclonal, neoAg-specific T-cell responses with effector-memory characteristics, providing mechanistic data consistent with the clinical benefit observed in pts with melanoma."

Clinical • IO biomarker • Tumor-specific neoantigens • Melanoma • Solid Tumor • CD8 • GZMB • IFNG • LAMP1 • TNFA

Intismeran autogene: "Intismeran plus pembrolizumab demonstrated durable and clinically significant improvements in RFS and DMFS vs standard-of-care pembrolizumab in high-risk resected melanoma at 5-years of follow-up"; Melanoma (Moderna) - Oncology Meeting

P2b data • Melanoma • Oncology

Cancer Vaccine Sustains 49 Percent Melanoma Reduction After 5 Years (PRNewswire) - "Results of the phase 2b trial, known formally as KEYNOTE-942, are being presented at the 2026 annual meeting of the American Society of Clinical Oncology on June 1 in Chicago, and simultaneously published in the society's Journal of Clinical Oncology...After five years of follow-up, 68.8 percent of patients who took the combination therapy remained cancer free while 49.1 percent of the patients in the pembrolizumab-alone group had no signs of cancer This means that adding intismeran to pembrolizumab reduced the risk for recurrence or death by 49 percent. The combination therapy also reduced the risk of distant metastasis — the spread of cancer to another part of the body — by 59 percent. Overall survival, meaning no death from cancer or any other cause, was 92.2 percent for the vaccine with immunotherapy group, while for the immunotherapy-alone group it was 71.3 percent."

P2b data • Melanoma