ASCO 2025 | Targeting DNA methylation enhances immunotherapy response in PD-1 resistant melanoma
Anna Maria Di Giacomo, MD, University Hospital of Siena, Siena, Italy, explains that targeting DNA methylation in PD-1 resistant melanoma can induce strong tumor immune modulation, making the tumor more immunogenic and susceptible to anti-PD-1 therapy. Dr Di Giacomo highlights the success of the Phase I NIBIT-M4 trial (NCT02608437) combining a hypomethylating agent with anti-CTLA-4 in previously treated melanoma patients, demonstrating safety, feasibility, and immunomodulatory activity. This led to the design of the randomized Phase II NIBIT-ML1 trial (NCT04250246), presented at the 2025 ASCO Meeting, to further explore the potential of this combination therapy. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
In the last, I think, 20 years, we have clearly demonstrated that epigenetic drugs and mainly the hypomethylating drugs are able to induce a strong tumor immune modulation to make the tumor more immunogenic and so able to be targeted by the anti-PD-1 or immune checkpoint therapy. So in the last few years, we have designed and conducted a phase one trial that for the first time demonstrated the potential of a combination of a hypomethylating agent, so an epigenetic drug with anti-CTLA-4 in melanoma...
In the last, I think, 20 years, we have clearly demonstrated that epigenetic drugs and mainly the hypomethylating drugs are able to induce a strong tumor immune modulation to make the tumor more immunogenic and so able to be targeted by the anti-PD-1 or immune checkpoint therapy. So in the last few years, we have designed and conducted a phase one trial that for the first time demonstrated the potential of a combination of a hypomethylating agent, so an epigenetic drug with anti-CTLA-4 in melanoma. Clearly, we have demonstrated the safety, feasibility, but also the immunomodulatory activity in patients previously treated with immune checkpoint in melanoma. So, based on these results, we have designed a phase two randomized trial we have presented at ASCO this year.
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