Moderna's mRNA-4359 Shows Promise in Melanoma Patients Failed by Checkpoint Inhibitors

Moderna has unveiled encouraging phase 1/2 data for its cancer candidate mRNA-4359, demonstrating efficacy in melanoma patients who had previously failed checkpoint inhibitor therapy. The results, set to be presented at the 2025 European Society for Medical Oncology Congress, highlight the potential of Moderna's mRNA technology in oncology and offer hope for patients with limited treatment options.

Promising Results in Advanced Melanoma

The study involved 29 patients with relapsed or refractory melanoma who had progressed after at least one PD-1/L1 checkpoint inhibitor treatment. Moderna evaluated two doses of mRNA-4359, which encodes both PD-L1 and IDO antigens, in combination with Merck & Co.'s Keytruda.

Key findings from the trial include:

• An objective response rate of 24% in evaluable patients
• A disease control rate of 60% when including patients with stable disease
• Responses observed in six out of nine evaluable patients with PD-L1-positive tumors

The treatment regimen consisted of intramuscular administration of mRNA-4359 every three weeks for up to nine doses. While the median duration of response has not yet been reached, these initial results are prompting further investigation into the therapy's potential.

Dual Mechanism of Action Sets mRNA-4359 Apart

Dr. Kyle Holen, head of development, therapeutics and oncology at Moderna, emphasized the unique approach of mRNA-4359: "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."

The dual targeting of PD-L1 and IDO is designed to both train the immune system to attack tumors and address the immunosuppression that can limit the effectiveness of immune responses. This strategy differentiates mRNA-4359 from existing treatments and may offer a new avenue for patients who have exhausted other options.

Renewed Interest in IDO Inhibition

The positive data from Moderna's trial has reignited interest in IDO as a therapeutic target. Despite previous setbacks in the field, including the failure of Incyte's epacadostat and IO Biotech's recent phase 3 disappointment, Moderna's approach appears to be yielding promising results.

Rose Loughlin, Ph.D., executive vice president of research at Moderna, commented on the competitive landscape, noting that while IO Biotech's recent data helped derisk mRNA-4359, there are significant differences between the two companies' platforms and antigens. This distinction has encouraged Moderna to "continue aggressively developing in that space," according to Loughlin.

As the pharmaceutical industry continues to explore novel combinations and targets in immuno-oncology, Moderna's mRNA-4359 represents a potentially significant advancement in the treatment of advanced melanoma and possibly other cancer types. The company's ongoing development of this candidate will be closely watched by both the scientific community and patients seeking new treatment options.