BioNTech announced October 13, 2026, that the phase 2/3 AHEAD-MERIT trial did not meet its first dual primary endpoint of progression-free survival (PFS) for the investigational mRNA cancer immunotherapy BNT113 (tenumomeran/raplemomeran, or "tenu-ra") combined with pembrolizumab, compared with pembrolizumab alone, as first-line treatment for unresectable recurrent or metastatic human papillomavirus 16 (HPV16)-positive head and neck squamous cell carcinoma (HNSCC) expressing programmed cell death ligand 1 (PD-L1).¹ The trial's independent data monitoring committee (IDMC) recommended that AHEAD-MERIT continue as planned to evaluate the second dual primary endpoint, overall survival (OS).¹
Key facts
- Drug: BNT113 (tenumomeran/raplemomeran, "tenu-ra"); BioNTech
- Class: mRNA cancer immunotherapy encoding HPV16 E6/E7 antigens, given with pembrolizumab
- Indication studied: First-line, unresectable recurrent/metastatic HPV16-positive HNSCC with PD-L1 CPS ≥1
- Trial: AHEAD-MERIT (NCT04534205); phase 2/3, open-label, 2-arm, approximately 285 patients
- Primary endpoint 1: Progression-free survival did not show a statistically significant improvement vs pembrolizumab alone
- Primary endpoint 2: Overall survival analysis ongoing; trial continues per IDMC recommendation
- Regulatory status: BNT113 holds FDA fast track designation (granted January 2026)
- Current approval: No HPV-targeted treatments currently approved for HNSCC
Under the trial's pre-specified statistical design, a statistically significant improvement in OS would establish a positive trial outcome even though the PFS endpoint was not met.¹
"The potential of mRNA cancer immunotherapies in combination regimen lies in their ability to induce immune responses that may translate into durable clinical benefit and, ultimately, prolonged survival of patients,” said Özlem Türeci, MD, co-founder and chief medical officer, BioNTech, in a company press release.¹ “While the PFS result was not statistically significant at this first analysis, the data support continued evaluation of BNT113 plus pembrolizumab in this trial and show that it is engaging its intended therapeutic mechanism. As immune-mediated anti-tumor effects build and deepen over time, the analysis of the second dual primary endpoint, overall survival, will be critical to fully assess the potential of this approach to deliver durable benefit for patients with HPV-driven head and neck cancer."
What does the AHEAD-MERIT trial involve?
AHEAD-MERIT (NCT04534205) is an open-label, 2-arm trial testing BNT113 plus pembrolizumab against pembrolizumab monotherapy, with an initial non-randomized safety run-in followed by a randomized comparison in about 285 patients.¹,² Because the trial is open-label, treatment assignment is not concealed from patients or investigators, though the dual primary endpoints rely on survival and imaging-based progression criteria rather than subjective assessment.² Patients are treated for up to approximately 24 months, with secondary endpoints including safety, objective response rate, and duration of response.¹ BioNTech said it remains blinded to ongoing trial data under the trial's governance procedures.¹
How does BNT113 work, and why target HPV16?
BNT113 is a messenger RNA (mRNA) cancer immunotherapy that encodes the HPV16 E6 and E7 proteins, antigens frequently expressed on HPV16-positive tumor cells, and is designed to induce HPV16-specific antitumor immune responses that enhance checkpoint inhibitors such as pembrolizumab.¹ Roughly one-third of HNSCC cases are HPV-positive, and HPV16 drives the large majority of HPV-positive oropharyngeal tumors, the most common HNSCC subtype.¹,³ No HPV-targeted treatments are currently approved, despite the distinct biology of HPV-positive tumors.¹
