Moderna has shared some of the phase 1/2 data that persuaded it to expand and prioritize development of a cancer candidate, reporting responses in melanoma patients failed by checkpoint inhibitors.
The data, which Moderna will present at the 2025 European Society for Medical Oncology Congress later this week, come from 29 patients with relapsed or refractory melanoma. All the patients had advanced after trying at least one PD-1/L1 checkpoint inhibitor. Moderna studied two doses of mRNA-4359, which encodes PD-L1 and IDO antigens, in combination with Merck & Co.’s blockbuster oncology drug Keytruda.
The objective response rate was 24% in evaluable patients who received mRNA-4359 intramuscularly every three weeks for up to nine doses. Adding in patients with stable disease resulted in a 60% disease control rate. The trial is yet to reach the median duration of response.
Moderna saw responses in six of the nine evaluable patients with PD-L1-positive tumors. Keytruda’s label in melanoma covers all levels of PD-L1, but an expression threshold applies in some other tumor types. Moderna said the subgroup analysis supports PD-L1 as a potential predictive biomarker in a high unmet need population.
The data drop follows the publication of monotherapy data last year. Moderna sees targeting PD-L1 and IDO as a way to train the immune system to kill a tumor and tackle the immunosuppression that can limit the impact of immune attacks. Kyle Holen, M.D., head of development, therapeutics and oncology at Moderna, set out how the dual mechanism of action differentiates mRNA-4359 from existing drugs.
“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,” Holen said in a statement. “This could enable broader and more durable immune responses for patients who have not had success with prior lines of therapy.”
Multiple companies have identified IDO as a target that could complement PD-1/L1 drugs, but the failure of Incyte’s epacadostat triggered a retreat from programs focused on the enzyme. IO Biotech was among the companies that continued to see a future for IDO. However, a phase 3 study of IO’s cancer vaccine missed its primary endpoint in August, and the FDA later advised the biotech against seeking approval.
Rose Loughlin, Ph.D., executive vice president of research at Moderna, commented on the competition at a Bernstein event last month. Noting differences between Moderna and IO’s platforms and antigens, Loughlin said the rival data helped derisk mRNA-4359 and encouraged the mRNA specialist “to continue aggressively developing in that space.”