mRNA Therapy/Anti-PD-L1 Therapy Combo Meets Primary Endpoint in ORR Over Historical Control
BioNTech is evaluating BNT111 in a phase 2 trial, primary analysis data from which will be presented in a future medical conference.
Prof. Özlem Türeci, MD
Credit: Wikipedia
BioNTech’s phase 2 clinical trial (NCT04526899) evaluating BNT111 mRNA therapy in participants with unresectable stage III or IV melanoma whose disease had progressed following anti-PD-L1 therapy has met its primary endpoint.1
The therapy demonstrated a statistically significant improvement in overall response rate (ORR) in patients treated in combination with cemiplimab, an anti-PD-1 monoclonal antibody being developed by Regeneron, as compared with historical control.1
“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,” Prof. Özlem Türeci, MD, Chief Medical Officer and cofounder, BioNTech, said in a statement.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.”
The trial is also assessing BNT111 and cemiplimab alone in monotherapy arms that each demonstrated clinical activity. The cemiplimab monotherapy arm had an ORR similar to the historical control of anti-PD-L1 or anti-CTLA-4 treatment. BioNTech and Regeneron plan to present data from the trial at a future medical conference. The trial dosed its first patient in June 2021.2
READ MORE: FDA Greenlights Lifileucel for Unresectable, Metastatic Melanoma Via Accelerated Approval
“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,” Türeci said in an earlier statement.2 “BNT111 has already shown a favorable safety profile and encouraging preliminary results in early clinical evaluation. With the start of patient treatment in our Phase 2 trial, we are encouraged to continue on our initial path to realize the potential of mRNA vaccines for cancer patients.”
The study is continuing to assess further follow-up, as well as secondary data that were not yet mature at the time of primary analysis. These secondary endpoints include ORR in both monotherapy arms, duration of response, disease control rate, time to response, and progression-free survival until24 months after treatment; overall survival until 48 months after treatment; incidence and severity of adverse events (AEs), occurrence of immune-mediated AEs, and occurrence of dose reductions/discontinuations until 27 months post treatment; changes in laboratory parameters and vital signs, change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) items scores, and time to deterioration in EORTC QLQ C30 scores.
BNT111 is based on BioNTech’s FixVac platform thati is designed to trigger an innate and tumor-antigen-specific immune response against cancer cells expressing 1 or more of a fixed combination of 4 mRNA-encoded, tumor-associated antigens.
