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

Intismeran autogene (V940/mRNA-4157) + pembrolizumab versus pembrolizumab alone as first-line therapy for advanced melanoma: the phase 2 INTerpath-012 study (ESMO 2025) - No abstract available

Clinical • Metastases • P2 data • Melanoma • Oncology • Solid Tumor

KEYNOTE-603: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=242 | Recruiting | Sponsor: ModernaTX, Inc. | Trial completion date: Jun 2025 ➔ Aug 2027 | Trial primary completion date: Jun 2025 ➔ Aug 2027

Trial completion date • Trial primary completion date • Gastric Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR • TMB

Personalized precision: Revolutionizing cancer treatment with mRNA-based vaccines in melanoma therapy. (PubMed, Adv Immunol) - "Early clinical trials suggest pembrolizumab and mRNA-4157/V940 may boost T cell-mediated cancer killing. Knowing the status and problems of melanoma therapeutic mRNA cancer vaccines in clinical trials is critical. In this chapter, we have focused on preclinical and clinical advances that have revealed mRNA melanoma vaccine manufacturing issues and solutions."

IO biomarker • Journal • Review • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor • PD-1 • PD-L1 • PD-L2

INTerpath-011: phase 2 study of intismeran autogene (V940/mRNA-4157) plus bacillus Calmette-Guérin (BCG) versus BCG alone for high-risk (HR) non–muscle-invasive bladder cancer (NMIBC) (ESMO 2025) - No abstract available

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

Intismeran autogene: Regulatory filing for adjuvant melanoma through 2028 (Moderna) - Q2 2025 Results

Filing • Melanoma • Oncology

Research and Clinical Progress of Therapeutic Tumor Vaccines. (PubMed, Vaccines (Basel)) - "For instance, the rapidly advancing mRNA-4157 vaccine is a typical representative that combines personalized antigens with efficient delivery vectors (lipid nanoparticles, LNPs), and it also shows synergistic advantages in melanoma patients treated in combination with immune checkpoint inhibitors. In this article, we will systematically discuss the current research and development status and clinical research progress of various therapeutic cancer vaccines."

Journal • Review • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor

Moderna Announces Data to be Presented at ESMO Congress 2025 (ACCESS Newswire) - "Moderna, Inc...announced that three abstracts on its investigational mRNA therapeutics have been accepted for presentation at the 2025 European Society for Medical Oncology (ESMO) Congress, which will be held October 17-21, 2025 in Berlin, Germany. This includes a mini oral presentation on mRNA-4359, Moderna's investigational mRNA-based therapy designed to elicit T-cell immune responses against tumor and immunosuppressive cells, as well as two poster presentations on intismeran autogene (V940/mRNA-4157)."

P1/2 data • Trial status • Bladder Cancer • Melanoma • Solid Tumor

Melanoma Vaccines: Comparing Novel Adjuvant Treatments in High-Risk Patients. (PubMed, Vaccines (Basel)) - " This review compares two promising personalized therapeutic cancer vaccine trials in advanced melanoma: Elios Therapeutics' Tumor Lysate (TL) vaccine and Moderna's mRNA-4157 vaccine...Key differences between the two trials include the use of CPIs, with 100% of patients in the mRNA trial receiving pembrolizumab versus 37% of the patients in the TL trial receiving either an anti-PD-1 or anti-CTLA-4... While both vaccines demonstrated promising efficacy, future phase 3 trials are needed to further evaluate their potential as adjuvant therapies for melanoma. This review highlights the comparative strengths and limitations of these vaccine platforms, providing insight into the evolving landscape of adjuvant cancer vaccines."

Journal • Review • Melanoma • Oncology • Solid Tumor

Current Progress and Future Perspectives of RNA-Based Cancer Vaccines: A 2025 Update. (PubMed, Cancers (Basel)) - "Recent clinical breakthroughs, particularly the success of mRNA-4157 combined with pembrolizumab in melanoma patients, have demonstrated significant improvements in efficacy, with a 44% reduction in recurrence risk compared to checkpoint inhibitor monotherapy. Non-coding RNA applications, including microRNA and long non-coding RNA therapeutics, represent emerging frontiers with potential for enhanced immune modulation. With over 60 candidates in clinical development and the first commercial approvals anticipated by 2029, RNA cancer vaccines are positioned to become cornerstone therapeutics in personalized oncology, offering transformative hope for cancer patients worldwide."

Journal • Review • Brain Cancer • Glioblastoma • Immune Modulation • Immunology • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor

A Clinical Study of V940 and Pembrolizumab (MK-3475) in People With Melanoma (V940-012/INTerpath-012) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor

Antigen vaccines in melanoma: Towards a new therapeutic paradigm (PubMed, Bull Cancer) - "The aim of this review article is to provide an overview of recent developments and prospects for antigen vaccines in the treatment of melanoma. We will explore their mechanism of action, the results of recent clinical trials, and the limitations and challenges of this new therapeutic approach."

Journal • Review • Melanoma • Oncology • Solid Tumor

A Clinical Study of V940 and Pembrolizumab (MK-3475) in People With Melanoma (V940-012/INTerpath-012) (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Melanoma • Oncology • Solid Tumor

Moderna Reports First Quarter 2025 Financial Results… (Moderna Press Release) - "COVID-19: The Company reported $84 million in Spikevax sales in the first quarter of 2025, which includes $29 million of U.S. sales and $55 million of international sales. As previously reported, Moderna entered into a tender opportunity in January to compete for COVID vaccine business in the EU; RSV: The Company reported $2 million in mRESVIA sales in the first quarter of 2025. Moderna's RSV vaccine for adults aged 60 years and older has been recently approved in Australia, Switzerland, Taiwan and the UK....Research and development expenses for the first quarter of 2025 decreased by 19% to $856 million, compared to the first quarter in 2024. The decrease was primarily driven by lower clinical development costs across respiratory programs due to timing of trial activities and program wind-downs. This reduction was partially offset by increased investment in Moderna's individualized neoantigen therapy (mRNA-4157)...and norovirus programs."

Commercial • Sales • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Respiratory Syncytial Virus Infections

Dynamics of T cell and T cell receptor following mRNA-4157 (V940) plus pembrolizumab or pembrolizumab alone in resected melanoma from the mRNA-4157-P201 (KEYNOTE-942) trial (AACR 2025) - "Expansion of novel T cell clonotypes in peripheral blood was observed to a greater extent after mRNA-4157 + pembro compared to pembro alone, and the degree of novel expansion was associated with RFS."

IO biomarker • Melanoma • 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

INTerpath-004: A Study of Adjuvant V940 and Pembrolizumab in Renal Cell Carcinoma (V940-004). (clinicaltrials.gov) - P2 | N=272 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Clinical Study of V940 and BCG in People With Bladder Cancer (V940-011/INTerpath-011) (clinicaltrials.gov) - P2 | N=308 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. (PubMed, J Clin Med) - "PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma...mRNA vaccines, such as Moderna's mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue...This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events."

Journal • Review • Tumor-infiltrating lymphocyte • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

A Clinical Study of V940 and BCG in People With Bladder Cancer (V940-011/INTerpath-011) (clinicaltrials.gov) - P2 | N=308 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

Monotherapy • New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

David Braun, MD, on phase 2 trial of an individualized neoantigen therapy for RCC (Urology Times) - "In this video, David A. Braun, MD, PhD, describes background and design of the phase 2 INTerpath-004 trial (NCT06307431), which is assessing the safety and efficacy of a neoantigen targeting personalized cancer vaccine, V940, in patients with renal cell carcinoma."

Video • Renal Cell Carcinoma

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

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

ASCO GU 2025: INTerpath-004: A Phase 2, Randomized, Double-Blind Study of Adjuvant Pembrolizumab (Pembro) With V940 (mRNA-4157) or Placebo for Renal Cell Carcinoma (RCC) (UroToday) - "INTerpath-004 (NCT06307431) is a global, multicenter, randomized, double-blind, phase 2 trial designed to evaluate the efficacy and safety or adjuvant V940 plus pembrolizumab or placebo in participants with RCC who have undergone nephrectomy....A total of 272 patients will be randomly assigned in a 1:1 ratio to receive pembrolizumab (400 mg IV every 6 weeks for up to 9 cycles) in combination with either V940 (1 mg IM every 3 weeks for up to 9 doses) or placebo. Treatment will continue until unacceptable toxicity, disease recurrence, patient withdrawal, or an investigator’s decision. Randomization will be stratified by histology (clear cell vs. papillary) and disease risk (intermediate-high, high, or M1 NED)."

Trial status • Renal Cell Carcinoma

A Clinical Study of V940 Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005) (clinicaltrials.gov) - P1/2 | N=230 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2031 ➔ Oct 2031 | Trial primary completion date: Oct 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

INTerpath-007: A Study of (Neo)Adjuvant V940 and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007). (clinicaltrials.gov) - P2/3 | N=1012 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting | Trial completion date: May 2033 ➔ Mar 2026 | Trial primary completion date: Apr 2029 ➔ Mar 2026

Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer