BNT113 Garners Fast-Track Designation in PD-L1+ HPV16+ HNSCC

The FDA has granted fast track designation on the investigational mRNA immunotherapy BNT113 for the treatment of patients with human papillomavirus type 16 positive (HPV16+) head and neck squamous cell carcinoma (HNSCC) expressing programmed cell death ligand-1 (PD-L1), according to a news release from the manufacturer.¹

The decision was based on preliminary safety and efficacy data from the ongoing phase 2/3 AHEAD-MERIT trial (NCT04534205).

Trial Design

The open label, 2-arm trial evaluated BNT113 in combination with pembrolizumab (Keytruda) vs pembrolizumab monotherapy as first-line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with combined positive score (CPS) greater than or equal to 1.²

Part A featured an initial safety run-in phase to confirm the safety and tolerability of the immunotherapy at the selected dose level in combination with pembrolizumab.²

Part B is the randomized, pivotal phase designed to generate efficacy and safety data. Patients from part A will continue treatment in that arm and will not undergo further randomization. An optional prescreening phase in Part B allows for central testing of HPV16 DNA and PD-L1 expression.²

Patients in both arms will be treated with the combination or pembrolizumab monotherapy for approximately 24 months.

The FDA Fast Track process is designed to facilitate the development and expedite the review of new drugs and vaccines that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. There are currently no HPV-targeted treatments approved for patients with HPV16-positive HNSCC.

Mechanism of Action

BNT113 is an investigational mRNA cancer immunotherapy encoding the E6 and E7 proteins of HPV16, which are frequently found in HPV16-positive solid tumors. This mRNA cancer immunotherapy approach is designed to induce HPV16-specific anti-tumor immune responses, thereby aiming to enhance clinical responses in patients being treated with checkpoint inhibitor standard of care treatment.

Upon administration, these proteins are processed and presented to the immune system, activating CD8-positive and CD4-positive T cells to attack HPV16-positive cancer cells.

REFERENCES

1. BioNTech receives FDA fast track designation for mRNA cancer immunotherapy candidate BNT113 in HPV16+ head and neck cancer. News release. Biopharmaceutical New Technologies. January 21, 2026. Accessed January 21, 2026. https://tinyurl.com/a2urj2x5

2. A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 (AHEAD-MERIT). https://www.clinicaltrials.gov/study/NCT04534205