Moderna Presents Promising Early Data for Its Investigational Cancer Antigen Therapy at the 2025 European Society for Medical Oncology Congress

Rhea-AI Summary

Moderna (NASDAQ:MRNA) will present early clinical, safety and translational data for investigational cancer antigen therapy mRNA-4359 at ESMO 2025 (Oct 17-21).

In a Phase 1/2 study of 29 checkpoint inhibitor‑resistant/refractory melanoma patients treated with mRNA-4359 plus pembrolizumab (400 µg, n=14; 1,000 µg, n=15), the objective response rate (ORR) was 24% and the disease control rate (DCR) was 60%. In PD-L1+ tumors (TPS≥1%, 9 evaluable), ORR was 67% (6 of 9). Median duration of response was not reached. The therapy advanced into the Phase 2 portion and showed a consistently manageable safety profile with no new immune-related adverse events. Presentation details and an investor webcast on Oct 17, 2025, are announced.

Positive

• ORR 24% across 29 evaluable CPI‑R/R melanoma patients
• DCR 60% across all evaluable patients
• ORR 67% in PD-L1+ subgroup (6 of 9 participants)
• mRNA-4359 advanced into Phase 2
• Safety: no new immune-related adverse events

Negative

• Small overall sample size: 29 patients
• Very small PD-L1+ subgroup: 9 evaluable patients
• Median duration of response not reached, limiting durability data
• Data are early and from an ongoing Phase 1/2 study (NCT05533697)

Insights

Clinical Trial Strategist

Early Phase 1/2 data show a signal of clinical activity for mRNA-4359, especially in PD-L1+ CPI‑refractory melanoma, and the program has moved into Phase 2.

mRNA-4359 plus pembrolizumab produced an overall objective response rate of 24% (29 patients evaluable) and a disease control rate of 60%. In the subset with PD-L1+ (TPS≥1%) disease the ORR was 67% (6 of 9), peripheral antigen-specific T cell responses were induced, novel T cell receptor clones appeared, and the median duration of response was not reached. These results are consistent with an early efficacy signal and support advancing the trial into the Phase 2 portion.

The clinical mechanism is clear in the data: the agent encodes epitopes for PD-L1 and IDO1 to generate antigen-specific T cells aimed at immune-escape pathways. Safety was reported as consistently manageable with no new immune-related adverse events, which matters for combination use with pembrolizumab. Key dependencies and risks remain: small cohort sizes (n=29 overall, n=9 PD-L1+ for the strongest signal) limit confidence in durability and generalisability, and the result set is early and non-randomized.

Watch items include the presentation at ESMO on October 17-21, 2025 (mini oral on October 17, 2025) for detailed data, the planned Phase 2 readouts following enrollment, and any expanded safety or durability metrics reported on the live webcast on October 17, 2025. These items will clarify reproducibility of the 67% PD-L1+ signal and the median duration of response.

mRNA-4359 has advanced into the Phase 2 portion of the ongoing Phase 1/2 trial

CAMBRIDGE, MA, 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:

• 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

• Time: Friday, October 17, 2025, 2:00 - 3:30 PM CET

• Location: Nuremberg Auditorium - Hall 5.2

• 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.

View the original press release on ACCESS Newswire

FAQ

What results did Moderna (MRNA) report for mRNA-4359 at ESMO 2025?

Moderna reported a 24% ORR and 60% DCR across 29 checkpoint inhibitor‑resistant/refractory melanoma patients; PD-L1+ tumors showed 67% ORR (6 of 9).

How large was the patient group for Moderna's mRNA-4359 ESMO 2025 data?

The presentation included data from 29 participants (400 µg n=14; 1,000 µg n=15), with 9 PD-L1+ evaluable patients.

Did Moderna report safety issues for mRNA-4359 plus pembrolizumab in the ESMO 2025 update?

Moderna reported a consistently manageable safety profile and no new immune-related adverse events for the combination.

What is the regulatory or trial status of mRNA-4359 after the ESMO 2025 data?

mRNA-4359 has advanced into the Phase 2 portion of the ongoing Phase 1/2 study (NCT05533697).

Will Moderna (MRNA) host an investor event to discuss the ESMO 2025 mRNA-4359 data?

Yes; Moderna will host a live webcast for investors and analysts on Oct 17, 2025 at 6:00 PM CET (12:00 PM ET), archived on its investor site for at least 30 days.