BNT111 Plus Cemiplimab Generates Responses in Unresectable Stage III/IV Melanoma

Özlem Türeci, MD

BioNTech has announced positive topline findings from an ongoing phase 2 trial (NCT04526899) evaluating the investigational mRNA cancer immunotherapy BNT111 in combination with cemiplimab (Libtayo) for patients with unresectable stage III or IV melanoma who experienced disease progression following anti-PD-(L)1 therapy.¹

The study met its primary efficacy end point of objective response rate (ORR), showing a statistically significant improvement in ORR among patients who received BNT111 plus cemiplimab vs historical controls. Moreover, both monotherapy arms displayed clinical activity; the ORR in the cemiplimab monotherapy arm was comparable with historical controls of anti–PD-(L)1 or anti–CTLA-4 therapies in this patient population. The findings will be presented at an upcoming medical meeting and will also be submitted for publication in a peer-reviewed scientific 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,” Özlem Türeci, MD, chief medical officer and co-founder of BioNTech, said 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. 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.”

BNT111 is an off-the-shelf cancer immunotherapy candidate intended for intravenous administration. The agent encodes for a fixed set of 4 non-mutated melanoma-associated antigens—NY-ESO-1, MAGE-A3, tyrosinase, and TPTE—delivered as a uridine mRNA-lipoplex formulation. BNT111 is designed to trigger an innate and tumor antigen–specific immune response against cancer cells expressing at least 1 of these tumor antigens.¹

Positive data with BNT111 follow the FDA’s November 2021 decision to grant fast track designation to the agent in combination with cemiplimab for the treatment of patients with unresectable stage III or IV melanoma who are relapsed/refractory to anti-PD-1 therapy. In the same year, BNT111 received orphan drug designation in stage IIB to IV melanoma.^1,2

The ongoing open-label, multicenter phase 2 study is examining BNT111 plus cemiplimab in patients with unresectable stage III or IV melanoma who are relapsed/refractory to anti–PD-(L)1 therapy. Patients are required to be at least 18 years of age, have received at least 1 but no more than 5 lines of prior therapy for advanced disease, be able to tolerate additional to anti–PD-(L)1 therapy, have known BRAF mutation status, and have an ECOG performance status of 1 or less.³

Eligible patients are randomly assigned 2:1:1 to receive BNT111 plus cemiplimab, BNT111 monotherapy, or cemiplimab monotherapy. Patients in the monotherapy arms who experience disease progression may be offered the addition of the other compound to their ongoing treatment.

Secondary end points included ORR in the monotherapy arms, duration of response, disease control rate, time to response, progression-free survival, and safety.

Additional findings from the phase 2 study showed that the safety profile of BNT111 in combination with cemiplimab was tolerable and consistent with prior clinical trial data evaluating BNT111 in combination with anti–PD-(L)1 regimens. Secondary end points were not mature at the time of the primary analysis; the study will continue as planned to examine these outcomes.¹

References

1. BioNTech announces positive topline phase 2 results for mRNA immunotherapy candidate BNT111 in patients with advanced melanoma. News release. BioNTech SE. July 30, 2024. Accessed July 30, 2024. https://investors.biontech.de/news-releases/news-release-details/biontech-receives-fda-fast-track-designation-its-fixvac#:~:text=MAINZ%2C%20GERMANY%2C%20November%2019%2C,potential%20treatment%20of%20advanced%20melanoma.
2. BioNTech Receives FDA fast track designation for its FixVac candidate BNT111 in advanced melanoma.News release. BioNTech SE. November 19, 2021. Accessed July 30, 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. Updated March 6, 2024. Accessed July 30, 2024. https://clinicaltrials.gov/study/NCT04526899