Melanoma: 'fixed' mRNA vaccine doubles hopes in most severe patients

For the first time, a 'fixed' mRNA vaccine, which is easier and cheaper to produce than custom vaccines, has been shown to double the response rate in patients with advanced melanoma resistant to multiple standard treatments, both in combination with immunotherapy (cemiplimab) and alone. This was announced by Paolo Ascierto, full professor of Oncology at the Federico II University of Naples and director of the Melanoma Oncology, Oncology Immunotherapy and Innovative Therapies Unit at the Pascale Institute in Naples, at the annual congress of the European Society For Medical Oncology (ESMO), being held in Berlin.

"BNT111 is a therapeutic vaccine based on messenger RNA (mRNA) technology, made famous by the vaccines developed against Covid-19," Ascierto explains. "But in this case, it is not about preventing a virus, but treating a tumor, melanoma. It is a fixed vaccine, because it is not tailored to the unique mutations of an individual patient. It is standardized to target a set of four antigens (proteins) that are present in most melanomas. The vaccine provides patients' cells with a kind of 'instruction manual,' in the form of mRNA, to teach the immune system to recognize and destroy cancer cells expressing those four specific proteins."

The study involved 184 patients with inoperable advanced melanoma (stage III or IV), who had already undergone and failed immune-blocking therapies such as anti-PD-(L)1, known to remove the 'brakes' that prevent the immune system from recognizing and fighting the cancer. The main outcome measured, namely the so-called objective response rate (ORR), was surprising, far exceeding expectations. "The combination of BNT111 and the immunotherapy cemiplimab achieved a target response rate of 18 percent, almost double the historical rate of 10 percent that is expected in this patient population, demonstrating the statistical efficacy of the new approach," Ascierto says. "A complete response, an exceptional result in oncology, was observed in 11.7 percent of patients treated with the combination. While follow-up data show deep and durable responses, with a positive impact on long-term survival as well: almost half of the patients (47.8%) treated with the BNT111 + cemiplimab combination were still alive at 24 months (2 years), and about a quarter of the patients (25%) treated with the combination were free of tumor progression at 24 months."

The results recorded in patients given only the fixed vaccine were also interesting. "Administration of the 'fixed' vaccine alone achieved a target response rate of 17 percent," Ascierto points out. Complete response (CR) was observed in 13 percent of patients treated with monotherapy. While follow-up data also show a positive impact on long-term survival: 37.6 percent of patients were still alive at 24 months, and during the same 2-year period, 21 percent were free of tumor progression."

Administration of the vaccine, both alone and in combination, proved to be well tolerated with a manageable safety profile. The most common effects were fever and chills.

"These data confirm the potential of 'fixed' mRNA vaccines as new tools against advanced melanoma," Ascierto concludes. "In a population refractory to other treatments, seeing objective responses, including complete remissions, is an encouraging result. The next step will be to verify efficacy in larger studies."