Melanoma, so the 'fixed' mRNA vaccine doubles responses in severe patients

For the first time, a 'fixed' mRNA vaccine, which is simpler and cheaper to produce than customised vaccines, has been shown to double the response rate in patients with advanced melanoma resistant to multiple standard treatments, either in combination with immunotherapy or alone. This is the result of the phase 2 BNT111-01 study, presented at the annual congress of the European Society for Medical Oncology (Esmo) in Berlin.

BNT111 is a therapeutic vaccine based on messenger RNA technology, the same technology we encountered during the Covid-19 pandemic. But in this case, it is not preventing a virus, but treating a tumour: melanoma. It is called 'fixed' because it is not tailored to the unique mutations of each patient. It is a standardised scheme that targets a set of four antigens, i.e. proteins, 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 recognise 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 failed immune-blocking therapies such as anti-PD-(L)1, treatments known to remove the 'brakes' that prevent the immune system from recognising and fighting the cancer. The main outcome measured, the objective response rate, was surprising, far exceeding expectations.

The combination of BNT111 and the immunotherapy cemiplimab achieved a target response rate of 18%, almost double the historical rate of 10% expected in this patient population, demonstrating the statistical efficacy of the new approach.
A complete response, an exceptional result in oncology, was observed in 11.7% of patients treated with the combination. Follow-up data show profound 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, and about a quarter of the patients (25%) were free of tumour progression at two years.

Interesting results were also recorded in patients who received only the fixed vaccine. The administration of the vaccine alone achieved a target response rate of 17%. A complete response was observed in 13% of patients treated with monotherapy. Here too, follow-up data show a positive impact on long-term survival: 37.6% of patients were still alive at 24 months, and 21% were free of tumour progression during the same period.