mRNA-based therapeutic cancer vaccine enters Phase II trial

The first patient has been treated with BioNTech’s messenger RNA (mRNA) BNT111 cancer vaccine in a Phase II trial. The study (NCT04526899) is evaluating an investigational therapeutic cancer vaccine candidate BNT111 in combination with Libtayo^® (cemiplimab) in patients with anti-PD1-refractory/relapsed unresectable Stage III or IV melanoma.

BNT111 is the lead product candidate from BioNTech’s FixVac platform. It targets a fixed combination of mRNA-encoded, tumour-associated antigens with the objective of triggering a strong and precise immune response against cancer and is fully owned by BioNTech.

The BNT111-01 trial, being conducted in collaboration with Regeneron, is approved by regulatory authorities in Spain, Germany, Italy, Poland, the UK, US and Australia. The open-label randomised trial will evaluate the efficacy, tolerability and safety of BNT111 in combination with Libtayo, an anti-PD-1 monoclonal antibody in 120 patients. The primary endpoint is the overall response rate of BNT111 in combination with Libtayo. Secondary endpoints include overall response rate in the single agent arms, duration of response and safety.

“Our vision is to harness the power of the immune system against cancer and infectious diseases. We were able to demonstrate the potential of mRNA vaccines in addressing COVID-19. We must not forget, that cancer is also a global health threat, even worse than the current pandemic,“ said Dr Özlem Türeci, Co-founder and Chief Medical Officer of BioNTech. “BNT111 has already shown a favourable safety profile and encouraging preliminary results in early clinical evaluation. With the start of patient treatment in our Phase II trial, we are encouraged to continue on our initial path to realize the potential of mRNA vaccines for cancer patients.”

BNT111 is an intravenous therapeutic cancer vaccine candidate encoding for a fixed set of four cancer-specific antigens optimised for immunogenicity and delivered as RNA-lipoplex formulation. More than 90 percent of melanomas in patients express at least one of the four tumour-associated antigens encoded in BNT111: NY-ESO-1, MAGE-A3, tyrosinase and TPTE. BNT111 is one of the most advanced of five clinical-stage FixVac product candidates within BioNTech’s development pipeline.

The Phase II trial is based on previous results from the Phase 1 Lipo-MERIT dose escalation trial that demonstrated a favourable safety profile in 89 patients with advanced melanoma. In addition, an analysis of efficacy from the Lipo-MERIT study in a subset of 42 metastatic melanoma patients previously treated with a checkpoint-inhibitor (CPI) showed that BNT111 mediated durable responses, both as a single agent and in combination with anti-PD-1 antibodies, and that durable objective responses by BNT111 were associated with activation and strong expansion of tumour-antigen-specific CD4+ and CD8+ T cells. These results were published in Nature in 2020.

The company also plans to start randomised Phase II trials with mRNA vaccine product candidates in two additional programs in 2021 (FixVac: BNT113 and iNeST: BNT122).