BNT113 Granted Fast Track Designation in HPV16-Positive HNSCC

The FDA has granted an investigational mRNA cancer immunotherapy, BNT113, fast track designation for the treatment of patients with unresectable recurrent or metastatic human papillomavirus type 16 (HPV16)-positive head and neck squamous cell carcinoma (HNSCC), according to a news release from the developer, BioNTech.¹

Efficacy data supporting the agency’s decision are derived from the phase 2/3 AHEAD-MERIT trial (NCT04534205), in which the investigational immunotherapy was assessed with pembrolizumab (Keytruda) vs the latter alone among patients with PD-L1–expressing, HPV16-positive HNSCC. Therein, the combinatory regimen was well tolerated and exhibited immune responses, as well as preliminary antitumor efficacy, in a poster presented at theEuropean Society for Medical Oncology (ESMO) Congress 2024.²

Specifically, among 3 patients who provided peripheral blood mononuclear cells (PBMCs) treated in the biomarker cohort, vaccine-induced T-cell responses were observed in 2 (66.7%) against the E6 and E7 peptides of HPV16. Additionally, the expansion of de novo and pre-existing T-cell receptor clonotypes was observed across all 3 patients in this cohort following vaccination.

Furthermore, 2 patients had E7 antigen-specific CD8-positive T cells appearing de novo by CD38 that were detectable until the end of treatment following MHC-I-multimer staining of PBMCs. Increasing CD45RA positivity and an effector memory phenotype were observed in a significant proportion of vaccine antigen-specific multimer CD8-positive T cells.

Regarding preliminary activity, among 15 patients treated with at least 1 dose of BNT113, 4 experienced a complete response and 2 experienced a partial response as best response, for an unconfirmed objective response rate (ORR) of 40% per blinded independent committee review (BICR). The unconfirmed disease control rate (DCR) per BICR was 53.3%, with an investigator-assessed unconfirmed ORR of 33.3% and DCR of 60.0%.

The median progression-free survival (PFS) per BICR was 3.9 months (95% CI, 2.1-10.6), with respective 6-, 12-, and 18-month rates of 42.3%, 14.1%, and 14.1%. Per investigator, the median PFS was 6.0 months (95% CI, 2.3-10.4), and the median overall survival (OS) was 22.6 months (95% CI, 9.8-not estimable [NE]).

“This analysis of the safety run-in cohort of AHEAD-MERIT confirmed that the combination of BNT113 and pembrolizumab was well tolerated; [treatment-emergent adverse effects (TEAEs)] were mostly grade 1 to 2,” lead author Nabil F. Saba, MD, FACP, professor and vice chair for Quality and Safety at the Department of Hematology and Medical Oncology at Emory University School of Medicine, wrote in the presentation with study coinvestigators.² “BNT113 triggered an immune response, as evidenced by a post-vaccination increase of serum levels of CXCL10, IFNα, IFNγ, IL-10, IL-6, and TNFα.”

Patients with HPV16-positive disease located in the oropharynx, oral cavity, hypopharynx, and larynx in the phase 2/3 study were randomly assigned 1:1 to receive pembrolizumab every 3 weeks for up to 24 months with or without weekly BNT113 for 8 weeks and then every 3 weeks. Eligible patients also had measurable disease per RECIST v1.1 criteria, a PD-L1 combined positive score (CPS) of at least 1, and an ECOG performance status of 0 or 1.

Among 15 patients treated with at least 1 dose of BNT113, the median age was 66.0 years (range, 41-74), 100% were male, and 66.7% had an ECOG performance status of 0. Most patients had either metastatic (40.0%) or unresectable recurrent disease (40.0%), had received prior platinum-based chemotherapy in an earlier setting (73.3%), and had a primary site of disease in the oropharynx (86.7%). Moreover, an equal number of patients had a PD-L1 CPS of 20 or greater and from less than 20 to 1 (46.7% each).

The primary end points of the trial were OS and ORR for up to 48 months. Secondary end points included ORR per investigator, PFS, DCR, duration of response, and safety.

All patients treated with BNT113 experienced a TEAE or a treatment-related AE (TRAE). A total of 53.3% of patients experienced grade 3 or higher TEAEs, including 13.3% with treatment-related TEAEs; 46.7% experienced serious TEAEs. A total of 13.3% and 20.0% of patients experienced serious TEAEs related to BNT113 and pembrolizumab, respectively. One patient (6.7%) experienced a serious TEAE leading to death. TEAEs led to the discontinuation of pembrolizumab in 1 patient (6.7%).

The most common any-grade TEAEs included pyrexia (60.0%), chills (60.0%), fatigue (53.3%), and nausea (33.3%). Grade 3 TEAEs included anemia in 2 patients (13.3%) and single instances of pyrexia, fatigue, decreased appetite, abdominal pain, and hypercalcemia.

References

1. BioNTech Receives FDA Fast Track Designation for mRNA cancer immunotherapy candidate BNT113 in HPV16+ head and neck cancer. News release. BioNTech SE. January 21, 2026. Accessed January 22, 2026. https://tinyurl.com/ycxhmnsk
2. Saba NF, Klinghammer K, Castelluci E, et al. Exploratory efficacy and translational results from the safety run in of AHEAD-MERIT, a phase II trial of first line pembrolizumab plus the fixed-antigen cancer vaccine BNT113 in advanced HPV16+ HNSCC. Ann Oncol. 2024;35(suppl 2):627. doi:10.1016/j.annonc.2024.08.938