mRNA-4359 / Moderna - LARVOL DELTA

Updated study design of mRNA-4359-P101: cohort expansions in first-line and CPI-R/R melanoma and PD-L1-high first-line NSCLC (ESMO-IO 2025) - P1/2 | "Patients receive intramuscular mRNA-4359 with intravenous pembrolizumab in Arms 1b, 2b, and 2d, and with ipilimumab/nivolumab in Arm 2c. Enrollment is now ongoing in these expansion cohorts.Clinical trial identification NCT05533697.Legal entity responsible for the study Moderna Inc., Cambridge, MA, USA."

Clinical • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • IDO1 • PD-L1

Restoring immune responsiveness in periphery and tumor with mRNA-4359, an mRNA-based therapy encoding PD-L1 and IDO1 peptides, plus pembrolizumab in checkpoint inhibitor resistant/refractory melanoma (SITC 2025) - P1/2 | "Responders (n=4) exhibited greater increases in T cell infiltration compared to non-responders (n=11), with 6.2-fold and 1.9-fold higher levels for CD4 and CD8 T cells, respectively.Conclusions mRNA-4359 plus pembrolizumab may restore immune responsiveness in CPI-R/R melanoma by priming antigen-specific T cells, expanding de novo TCR clones, and creating a more inflamed TME with increased T cell infiltration, allowing for restoration of checkpoint inhibitor response.Acknowledgements This study was funded by Moderna, Inc.Ethics Approval The protocol and all amendments were approved by the appropriate institutional review board or independent ethics committee at each participating study site. The study was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines."

Checkpoint inhibition • IO biomarker • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IDO1

Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=361 | Recruiting | Sponsor: ModernaTX, Inc. | N=194 ➔ 361 | Trial completion date: Dec 2027 ➔ Feb 2032 | Trial primary completion date: Dec 2027 ➔ Feb 2032

Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ALK • EGFR • ROS1

Clinical outcomes and PD-L1 expression analyses from a trial of mRNA-4359 plus pembrolizumab in checkpoint inhibitor-resistant/refractory (CPI-R/R) melanoma (ESMO 2025) - P1/2 | "Treatment induced peripheral antigen-specific T-cell responses and emergence of novel TCR clones. Table: 1515MO Investigator-assessed ORR by baseline PD-L1 TPS on screening biopsies in response evaluable CPI-R/R melanoma patients ORR in response evaluable patients by baseline PD-L1 TPS mRNA-4359 (400 μg) + pembrolizumab (400 mg) (N=13) mRNA-4359 (1000 μg) + pembrolizumab (400 mg) (N=9) All Pts (N=22) PD-L1 TPS ≥1% 5/6 (83%) 1/3 (33%) 6/9 (67%) PD-L1 TPS <1% 0/7 (0%) 0/6 (0%) 0/13 (0%) Conclusions mRNA-4359 plus pembrolizumab demonstrated a favorable safety profile, T-cell responses and durable clinical activity in CPI-R/R melanoma pts with PD-L1 TPS ≥1%, supporting PD-L1 as a potential predictive biomarker in this high unmet need population."

Checkpoint inhibition • Clinical • Clinical data • IO biomarker • Melanoma • Oncology • Solid Tumor • IDO1 • PD-L1

Moderna…announced that clinical, safety and translational data from its Phase 1/2 study evaluating mRNA-4359 in combination with pembrolizumab in checkpoint inhibitor-resistant/refractory(CPI-R/R) melanoma patients will be presented at the 2025 European Society for Medical Oncology (ESMO) Congress (ACCESS Newswire) - "The presentation includes data from 29 participants with CPI-R/R melanoma who have had ≥1 prior checkpoint inhibitor (CPI) therapy....Across all evaluable patients, the objective response rate (ORR) was 24% and disease control rate (DCR), or the combination of patients achieving tumor response and stable disease, was 60%. Among those with response-evaluable disease and PD-L1+ (TPS≥1%) tumors, the ORR was 67% (6 of 9 participants), with treatment successfully inducing peripheral antigen-specific T cell responses and novel T cell receptor clones."

P1/2 data • Melanoma

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

First-in-human, phase I/II, monotherapy, dose-escalation study of mRNA-4359, an mRNA-encoded PD-L1/IDO1 antigen-specific therapy, in advanced/refractory solid tumors (ESMO 2024) - P1/2 | "mRNA-4359 monotherapy was well tolerated at all tested dose levels with observation of SD and detectable antigen-specific T cell response. Enrollment continues in the mRNA-4359 + pembrolizumab combination arms, followed by expansion cohorts in pts with melanoma and non-small cell lung cancer."

Metastases • Monotherapy • P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IDO1 • PD-L1

Experimental mRNA cancer vaccine shows potential for advanced stage cancer patients in Phase 1 trial (Eurekalert) - P1 | N=194 | NCT05533697 | Sponsor: ModernaTX, Inc. | "Interim data from the Phase I dose escalation part of the mRNA cancer immunotherapy (mRNA-4359), show promise in patients with advanced solid cancers...The investigational mRNA cancer immunotherapy is targeted for patients with lung cancer, melanoma and other solid tumours. Nineteen patients with advanced stage cancers received between one and nine doses of the immunotherapy treatment...Data also showed the mRNA immunotherapy could activate the immune system in many patients, generating immune cells in the blood that could recognise the two proteins of interest (PD-L1 and IDO1)....The trial continues to recruit patients with melanoma and lung cancer in combination with the immunotherapy drug pembrolizumab to provide more information on the safety and efficacy of the therapy."

Enrollment status • P1 data • Lung Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

New mRNA 'cancer vaccine' trial launches in UK (Live Science) - "An 81-year-old man from Surrey became the first patient in the U.K. to receive a new 'vaccine' designed to treat solid-tumor cancers, such as the skin cancer melanoma....The new vaccine being tested in the U.K. and elsewhere around the world is called mRNA-4359..."

New trial • Melanoma • Skin Cancer • Solid Tumor

Phase 1/2 study of mRNA-4359 administered alone and in combination with immune checkpoint blockade in adult participants with advanced solid tumors. (ASCO 2023) - P1/2 | "Arm 1b will be dose confirmatory and will run concurrently with a pharmacodynamic arm; both will assess mRNA-4359 in combination with pembrolizumab in patients with primary/secondary checkpoint inhibitor refractory locally advanced/metastatic melanoma or NSCLC. Study enrollment into Arm 1a has commenced in the United States and Australia with plans to open sites in Europe later in 2023. Clinical trial information: NCT05533697."

Checkpoint block • Checkpoint inhibition • Clinical • Combination therapy • Metastases • P1/2 data • Basal Cell Carcinoma • Bladder Cancer • Breast Cancer • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Immune Modulation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • IDO1

Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=194 | Recruiting | Sponsor: ModernaTX, Inc.

Checkpoint inhibition • Combination therapy • New P1/2 trial • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ALK • CD4 • CD8 • EGFR • FOXP3 • ROS1

Moderna Expands Its mRNA Pipeline with Three New Development Programs (Yahoo Finance) - "Moderna's new checkpoint cancer vaccine candidate (mRNA-4359) expresses Indoleamine 2,3-dioxygenase (IDO) and programmed death-ligand 1 (PD-L1) antigens. Moderna designed mRNA-4359 with the goal of stimulating effector T-cells that target and kill suppressive immune and tumor cells that express target antigens. Moderna is planning to explore initial indications for advanced or metastatic cutaneous melanoma and non-small cell lung carcinoma (NSCLC)."

Pipeline update • Cutaneous Melanoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor