BNT113 Plus Pembrolizumab Misses PFS End Point in HPV16+ HNSCC

Adding the investigational mRNA cancer immunotherapy tenumomeran/raplemomeran (BNT113) to pembrolizumab (Keytruda) did not significantly extend progression-free survival (PFS) over pembrolizumab alone in the frontline treatment of human papillomavirus 16 (HPV16)–positive head and neck squamous cell carcinoma (HNSCC).¹

The findings come from the first topline analysis of the phase 2/3 AHEAD-MERIT trial (NCT04534205), which is comparing the combination with pembrolizumab monotherapy in patients with unresectable recurrent or metastatic disease that expresses PD-L1. PFS is 1 of 2 dual primary end points in the phase 3 portion of the study; the other is overall survival (OS).

After reviewing the PFS analysis, the independent data monitoring committee (IDMC) advised that AHEAD-MERIT proceed as planned to the OS evaluation. BioNTech noted in a news release that, per the prespecified statistical plan, a statistically significant OS benefit on its own would be sufficient for a positive trial outcome despite the negative PFS finding. The company also stated that it remains blinded to the ongoing data under the study's governance procedures.

"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," Özlem Türeci, MD, cofounder and chief medical officer at BioNTech, stated in the news release.

Trial Design

AHEAD-MERIT is an open-label, multisite, 2-arm study with 2 components. Part A was a nonrandomized safety run-in intended to confirm that tenumomeran/raplemomeran can be safely combined with pembrolizumab at the chosen dose range. Part B, the randomized portion designed to generate pivotal efficacy and safety data, assigned patients in the first-line setting to either the combination or pembrolizumab alone.²

To enroll, patients must have unresectable recurrent or metastatic HPV16-positive HNSCC with a PD-L1 combined positive score (CPS) of 1 or higher. Treatment in either arm continues for up to approximately 24 months. Beyond the dual primary end points, secondary end points include safety, objective response rate (ORR), and duration of response (DOR).

Targeting HPV16 Oncoproteins

Tenumomeran/raplemomeran encodes the HPV16 E6 and E7 proteins, which are commonly expressed in HPV16-positive solid tumors.¹ According to BioNTech, the goal is to prime HPV16-specific antitumor immunity and, in turn, strengthen responses to checkpoint inhibition. The FDA granted fast track designation to the agent in January 2026.

The company emphasized that no HPV-targeted therapy has been approved to date, and that disease progression on current standard treatment is common among patients with HPV16-positive HNSCC. Roughly one-third of HNSCC cases are linked to HPV infection, and HPV16 accounts for the majority, the company noted.

Türeci framed OS as the more informative measure for an immune-based strategy. "As immune-mediated antitumor effects build and deepen over time, the analysis of the second dual primary end point, [OS], will be critical to fully assess the potential of this approach to deliver durable benefit for patients with HPV-driven head and neck cancer," she said.

REFERENCES

1. BioNTech Provides Update on Phase 2/3 Clinical Trial for mRNA Cancer Immunotherapy Candidate BNT113 in Metastatic HPV16-positive Head and Neck Cancer. News release. BioNTech. October 13, 2026. Accessed October 14, 2026. https://tinyurl.com/mrx5y2ps

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). ClinicalTrials.gov. Updated October 14, 2026. Accessed October 14, 2026. https://clinicaltrials.gov/study/NCT04534205