BioNTech has posted an early win for BNT111, linking a combination of the cancer immunotherapy candidate and Regeneron’s checkpoint inhibitor Libtayo to a better response rate than a historical control in melanoma patients.
Investigators randomized 184 patients with anti-PD-(L)1 refractory or relapsed, unresectable advanced melanoma to one of three cohorts. Half of the subjects in the open-label phase 2 trial received BNT111 and Libtayo, Regeneron’s anti-PD-1 drug, in combination. The remaining participants were split evenly into two cohorts that each received one of the molecules as a single agent.
BioNTech saw a statistically significant improvement in the overall response rate of the combination arm compared to historical control data, causing the study to hit its primary endpoint. Both monotherapy arms showed clinical activity, BioNTech said, with Libtayo performing in line with the historical control.
The partners plan to discuss the data, which were free from safety shocks, with regulators as they think through their plans for further development. The combination of BNT111 and Libtayo has FDA fast-track status in the melanoma population enrolled in the study.
It is unclear based on the little publicly available evidence whether the combination is a significant step forward. BioNTech and Regeneron are yet to share the response results, choosing to keep them back for an upcoming medical conference, and data on progression-free and overall survival were immature at the time of the analysis.
Even so, the early signs of efficacy are positive for BioNTech’s attempts to develop a cancer vaccine. BNT111 uses a different mRNA format than BioNTech’s COVID-19 vaccine, with the biotech using uridine mRNA chemistry rather than nucleoside-modified mRNA for the cancer candidate. BioNTech designed the non-coding backbone for oncology applications.
With BNT111, the biotech is using the technology to trigger T-cell responses against NY-ESO-1, MAGE-A3, tyrosinase and TPTE. More than 90% of patients with cutaneous melanomas express at least one of the antigens. By triggering responses against the antigens, BNT111 could reenergize anti-cancer attacks in patients failed by single-agent checkpoint inhibitors.
That promise led BioNTech and Regeneron to team up in 2020. The partners agreed to jointly fund a phase 2 trial of BNT111 and Libtayo. Each company retained full commercial rights to its molecule. The companies expanded the relationship to cover another asset, BNT116, in 2022.