On October 13, BioNTech announced the first top-line results of its AHEAD-MERIT Phase 2/3 clinical trial (NCT04534205) for its mRNA cancer immunotherapy candidate BNT113 .
Unfortunately, BNT113 in combination with pembrolizumab as first-line treatment for unresectable recurrent or metastatic HPV16-positive, PD-L1-positive head and neck squamous cell carcinoma failed to meet the first of the dual primary endpoints—progression-free survival —and did not statistically demonstrate a significant improvement over pembrolizumab monotherapy.
Following the announcement, BioNTech's stock price fell by about 6% during trading, casting a shadow over market enthusiasm for the mRNA tumor vaccine sector once again.
It is important to note that this setback does not equate to a complete failure of the trial. The independent data monitoring committee recommends that the trial proceed as planned and that the second dual primary endpoint—overall survival—be assessed.
According to the pre-specified statistical design of the trial, even if the progression-free survival (PFS) endpoint is not met, a positive trial result can still be established as long as overall survival (OS) shows a statistically significant improvement. BioNTech stated that it will continue to maintain data blinding in accordance with trial management guidelines.
The failure of BNT113 has drawn attention due to its previous success. As an off-the-shelf product on BioNTech's own FixVac platform, BNT113 encodes two oncoproteins, E6 and E7, which are commonly expressed in HPV16-positive tumors, and therefore does not require customized production for each patient like personalized vaccines.
In January of this year, the FDA granted Fast Track designation to the drug based on Phase II data, allowing it to be used as first-line treatment for patients with PD-L1-positive and HPV16-positive head and neck cancer. The Phase II data was initially encouraging: early results released in September 2024 showed an unconfirmed objective response rate (ORR) of 40% after 12 months of treatment with the drug in combination with pembrolizumab. However, from the Phase II safety introduction phase to the Phase III interim analysis, the efficacy signal ultimately failed to cross the statistical threshold.
For BioNTech, BNT113 is just one piece in its oncology portfolio. The company currently has more than 10 ongoing registration trials covering mRNA immunotherapy, immunomodulators, and antibody-drug conjugates, with several more late-stage data readouts expected by 2026, including BNT116 (in combination with cemiplimab) for non-small cell lung cancer.
Source: https://news.yaozh.com/archive/49162.html