323TiP Updated study design of mRNA-4359-P101: Cohort expansions in first-line and CPI-R/R melanoma and PD-L1-high first-line NSCLC
Year: 2025
Type: article
Abstract: Background Despite major advancements with immune checkpoint inhibitors (CPIs), many patients’ disease does not respond or ultimately relapses, underscoring the need for novel approaches. mRNA-4359 is an intramuscular mRNA-based cancer antigen therapy that encodes programmed death-ligand 1 and indoleamine 2,3-dioxygenase 1 (PD-L1/IDO1) peptides to stimulate antigen-specific T cells. These T cells are intended to target cancer and immunosuppressive cells to promote an immune-permissive tumor microenvironment. mRNA-4359 is being evaluated in combination with CPIs to potentially enhance anti-tumor activity. Trial Design mRNA-4359-P101 (NCT05533697) is an ongoing, phase I/II, open-label, first-in-human, non-randomized study evaluating mRNA-4359 alone or in combination with CPIs. Following completion of dose-escalation and dose-optimization, Protocol Amendment 3.0 (published 28 July 2025) added and/or expanded upon cohorts in melanoma and non-small cell lung cancer (NSCLC). Primary and secondary objectives include safety, tolerability, anti-tumor activity, and T cell profile changes. Expansion cohorts are: (Arm 2b) first-line advanced NSCLC with PD-L1 tumor proportion score (TPS) ≥50% and EGFR/ALK-negative (n=50); (Arm 2c) first-line advanced melanoma treated with ipilimumab/nivolumab (n=45); (Arms 1b and 2d) ≥ second-line CPI-resistant/refractory (CPI-R/R) melanoma with PD-L1 TPS ≥1% (combined planned n=97). 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.
Source: Immuno-Oncology Technology
Institutions: University of Birmingham, Edith Cowan University, Fiona Stanley Hospital, Hammersmith Hospital, University of Colorado Health, University of Colorado Cancer Center, University of Colorado Anschutz, Churchill Hospital, Melanoma Institute Australia, Massachusetts General Hospital, Washington University in St. Louis, Hackensack University Medical Center, Guy's Hospital, University of Chicago, Olivia Newton-John Cancer Research Institute, Southampton General Hospital, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, George Washington University, Henry Ford Health, Henry Ford Hospital, NHS Greater Glasgow and Clyde
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,340
OpenAlex ID: W7117295617
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