BioNTech's mRNA Immunotherapy BNT111 Yields Positive Topline Results in Advanced Melanoma

Image Credit: © Tobias Arhelger - stock.adobe.com

BioNTech recently announced positive topline results stemming from a phase 2 clinical trial exploring the combined efficacy of mRNA immunotherapy candidate BNT111 and anti-PD-1 monoclonal antibody cemiplimab (Libtayo; Regeneron Pharmaceuticals) in patients with advanced melanoma.¹

The combination of BNT111 and cemiplimab received a US Food and Drug Administration (FDA) Fast Track designation in 2021 for the very same indication.² BNT111, an off-the-shelf candidate for intravenous administration, received an Orphan Drug designation for stage IIB through IV melanoma in the same year.

The interventional clinical trial (NCT04526899)³ includes patients (n=184) who are at least 18 years of age who have a diagnosis of unresectable stage III or IV cutaneous melanoma with measurable disease, as confirmed by RECIST 1.1 criteria. All patients must have previously experienced image-verified disease progression despite receiving a minimum of 12 weeks of treatment on an approved anti-PD-1/PD-L1 regimen.

The study includes 3 experimental treatment arms. In the first arm, participants receive a combination of BNT111 and cemiplimab, with BNT111 administered via intravenous (IV) injection and cemiplimab given as an IV infusion. The second arm involves monotherapy with BNT111, provided through IV injection. The third arm focuses on cemiplimab monotherapy, which is delivered through an IV infusion.

The trial successfully met its primary endpoint by demonstrating a notable increase in the overall response rate for patients treated with BNT111 combined with cemiplimab, compared to historical data.

Both treatment groups receiving only 1 of these drugs also demonstrated clinical effectiveness. The overall response rate for cemiplimab alone matched expectations based on previous anti-PD-(L)1 or anti-CTLA-4 therapies.

The combination treatment was generally well-tolerated, and its safety profile was consistent with earlier studies involving BNT111 with similar therapies.

Data from these studies is set to be presented at a later scientific meeting. BioNTech and Regeneron have also shared plans to submit the data for publication in a peer-reviewed journal.

“These Phase 2 results mark a significant step towards our vision of personalized cancer medicine. 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,” said professor Özlem Türeci, MD, chief medical officer and co-founder at BioNTech, in a news release.¹

“These data are a proof of concept for us in three dimensions: First, for our decade-long improved mRNA cancer vaccine technology that uses uridine mRNA chemistry, a non-coding backbone that is engineered for optimal translational performance and our proprietary lipoplex formulation for delivery," Türeci said. "Second, for our computational approaches for selecting suitable tumor antigens for our cancer indication-specific FixVac platform candidates. Third, for our strategy to combine synergistic modalities, in this case BNT111 with an established immune checkpoint treatment.”

The study, which commenced in 2021, has an anticipated primary conclusion date of November 2025 and an estimated study conclusion date of July 2026.³

References

1. BioNTech announces positive topline phase 2 results for mRNA immunotherapy candidate BNT111 in patients with advanced melanoma. News release. BioNTech. July 30, 2024. Accessed July 31, 2024. https://investors.biontech.de/news-releases/news-release-details/biontech-announces-positive-topline-phase-2-results-mrna
2. BioNTech receives FDA fast track designation for its FixVac candidate BNT111 in advanced melanoma. News release. BioNTech. November 19, 2021. Accessed July 31, 2024. https://investors.biontech.de/news-releases/news-release-details/biontech-receives-fda-fast-track-designation-its-fixvac
3. Trial with BNT111 and cemiplimab in combination or as single agents in patients with anti-PD-1-refractory/​relapsed, unresectable stage III or IV melanoma. Clinicaltrials.gov. Accessed July 31, 2024. https://clinicaltrials.gov/study/NCT04526899