mRNA-4359 has advanced into the Phase 2 portion of the ongoing Phase 1/2 trial
CAMBRIDGE, MA / ACCESS Newswire / October 12, 2025 / Moderna, Inc. (NASDAQ:MRNA) today 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, October 17-21, 2025, in Berlin, Germany. mRNA-4359 is an investigational immune-evasion targeted cancer antigen therapy (CAT) that encodes epitopes of two common immune escape pathways, PD-L1 and IDO1, to elicit antigen-specific T cell responses that may directly kill tumor cells and deplete tumor suppressor cells.
The presentation includes data from 29 participants with CPI-R/R melanoma who have had ≥1 prior checkpoint inhibitor (CPI) therapy. Participants received the combination therapy at 400 µg (n=14) or 1,000 µg (n=15), given intramuscularly every three weeks for up to nine doses. 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. The median duration of response (DOR) was not reached. The improved efficacy in PD-L1+ patients supports PD-L1 as a potential predictive biomarker in this high unmet need population.
“While early, today’s mRNA-4359 melanoma data in highly CPI-refractory metastatic patients are unique in the field and incredibly promising for future development options. We are encouraged by its potential to address such a high unmet need for many patients,” said Dr. Kyle Holen, Head of Development, Therapeutics and Oncology, Moderna. “Where other checkpoint inhibitors restore non-specific T cell activity, mRNA-4359 encodes two critical immune escape pathways to help generate new, target-directed T cells. This could enable broader and more durable immune responses for patients who have not had success with prior lines of therapy. We are proud to present these data and to demonstrate the role our mRNA-based therapies could play in transforming the lives of those affected by cancer.”
mRNA-4359 in combination with pembrolizumab demonstrated a consistently manageable safety profile, with no new immune-related adverse events (AEs). mRNA-4359 continues to be evaluated in an ongoing phase 1/2 study (NCT05533697) as a monotherapy and in combination with pembrolizumab in patients with advanced melanoma and non-small cell lung cancer (NSCLC).
“After failing to respond to first-line immunotherapy, existing options for PD-L1+ patients are limited, underscoring a clear need for effective, tolerable therapies,” said Prof. David J. Pinato, Clinical Professor of Experimental Cancer Therapeutics at Imperial College London and Consultant Medical Oncologist at Imperial College Healthcare NHS Trust and lead author and presenter of the abstract. “mRNA-4359 has the potential to rebalance the tumor microenvironment to overcome this immunotherapy resistance. These data are encouraging as we continue to investigate the potential of mRNA-4359.”
The details of the presentation are as follows:
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Mini Oral Presentation #1515MO: Clinical Outcomes and PD-L1 Expression Analyses from a Trial of mRNA-4359 Plus Pembrolizumab in Checkpoint Inhibitor-Resistant/Refractory (CPI-R/R) Melanoma
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Time: Friday, October 17, 2025, 2:00 – 3:30 PM CET
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Location: Nuremberg Auditorium – Hall 5.2
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Presenter: David J. Pinato
Moderna’s Oncology Investor & Analyst Event
Moderna will host a live webcast for investors and analysts on Friday, October 17, 2025, at 6:00 PM CET (12:00 PM ET), which will be available under “Events and Presentations” in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna’s website for at least 30 days following the presentation.
About mRNA-4359
mRNA-4359 is an immune-evasion targeted cancer antigen therapy that encodes broad epitopes of PD-L1 and IDO1. With its dual mechanism of action, it elicits antigen-specific T-cell responses to simultaneously: (1) kill tumor cells expressing PD-L1 and IDO1, and (2) deplete immunosuppressive cells that shield the tumor from attack. This is hypothesized to rebalance the tumor microenvironment into an immune-permissive state, supporting sustained and durable anti-tumor activity with a manageable safety profile.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the potential of Moderna’s mRNA-based therapies for cancer patients; the potential of PD-L1 as a predictive biomarker; the response rate and safety profile of mRNA-4359; and the potential for mRNA-4359 to enable broader and more durable immune responses for patients who have not had success with prior lines of therapy. In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “could,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control, and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading “Risk Factors” in Moderna’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date of this press release.
Moderna Contacts
Media:
Chris Ridley
Head of Global Media Relations
+1 617-800-3651
Chris.Ridley@modernatx.com
Investors:
Lavina Talukdar
Senior Vice President & Head of Investor Relations
+1 617-209-5834
Lavina.Talukdar@modernatx.com
SOURCE: Moderna, Inc.
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