BioNTech and Regeneron will face off against Merck and Moderna, which are advancing their investigational cancer vaccine mRNA-4157/V940 in combination with Keytruda, in advanced melanoma.
BioNTech on Tuesday announced that its investigational mRNA cancer immunotherapy BNT111 hit its primary efficacy endpoint in a Phase II trial in advanced melanoma when combined with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab).
Compared with historical controls, BNT111 plus Libtayo led to a statistically significant improvement in overall response rate in patients with stage III or IV melanoma who had progressed after previous PD-(L)1 treatment. Monotherapy with BNT111 or Libtayo also showed clinical activity, according to Tuesday’s topline readout.
The combination regimen was well-tolerated with a safety profile consistent with previous studies.
BioNTech CMO and co-founder Özlem Türeci in a statement said that these early findings “mark a significant step” toward the company’s goal of developing personalized cancer therapies. “We envision mRNA as a centerpiece in future treatment paradigms for cancer, helping to address unmet medical needs, such as for patients with anti-PD-(L)1 refractory or resistant melanoma.”
BioNTech and Regeneron did not provide specific data in their announcement but promised to do so at an upcoming medical congress. The companies will also submit their data for publication to a peer-reviewed journal.
Designed using BioNTech’s proprietary FixVac platform, BNT111 is an investigational off-the-shelf mRNA cancer immunotherapy that encodes four proteins—NY-ESO-1, MAGE-A3, tyrosinase and TPTE—which are associated with melanoma. According to BioNTech, more than 90% of cutaneous melanoma cases are positive for at least one of these antigens.
In earlier-stage studies, BNT111 has shown that it can boost the immune system’s anti-tumor response, while also priming T cells against the antigen for at least one year, with the help of monthly vaccinations. In July 2020, the company published Phase I data for BNT111 in Nature, demonstrating the expansion and activation of tumor-antigen-specific T cells in response to BNT111 treatment, exhibiting strong activity against cancer cells.
Of the 17 patients in the early-stage study who were dosed with both BNT111 and an anti-PD-1 agent, six achieved partial treatment response.
Around the same time, BioNTech and Regeneron announced their immunotherapy collaboration, testing BNT111 with Libtayo in patients with unresectable stage III or IV cutaneous melanoma. Under the terms of the agreement, the companies will split development costs equally and retain full commercial rights over their respective products. Revenues will also be recorded separately.
With Wednesday’s topline data, BioNTech and Regeneron are poised to compete with Merck and Moderna, which are jointly working on a combination of mRNA-4157/V940, a personalized cancer vaccine, with Keytruda (pembrolizumab).
In December 2022, the partners reported that the regimen aced its Phase IIb trial, significantly cutting the risk of disease recurrence or death in patients with stage III/IV melanoma who had undergone resection but are at a high risk of recurrence. Merck and Moderna are currently running two Phase III trials for mRNA-4157/V490, one in melanoma and the other in non-small cell lung cancer.
