BNT113/Pembrolizumab Misses PFS End Point in HPV16+ Head and Neck Cancer

The investigational mRNA cancer immunotherapy BNT113 (tenumomeran/raplemomeran) in combination with pembrolizumab (Keytruda) did not demonstrate a statistically significant improvement in progression-free survival (PFS) vs pembrolizumab alone, missing the first of 2 dual primary end points in the phase 2/3 AHEAD-MERIT trial (NCT04534205), according to topline results announced by the developer, BioNTech.¹

The trial will continue as planned to evaluate its second dual primary end point of overall survival (OS). Under the study’s prespecified statistical design, a statistically significant improvement in OS would establish a positive trial outcome even though the PFS end point was not met.

What did the first AHEAD-MERIT analysis show?

At the analysis for PFS, BNT113 in combination with pembrolizumab did not demonstrate a statistically significant improvement in PFS vs pembrolizumab monotherapy as a first-line treatment for patients with unresectable recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC) expressing PD-L1. The Independent Data Monitoring Committee recommended that the trial continue as planned to evaluate the second primary end point of OS; developers remain blinded to ongoing trial data in accordance with the trial’s governance procedures. BioNTech did not report specific PFS data in the announcement.

“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,” said Özlem Türeci, MD, co-founder and chief medical officer at BioNTech, in the news release.¹

Why does the trial continue despite the PFS result?

The phase 3 part of AHEAD-MERIT was designed with dual primary end points of PFS and OS to provide complementary measures of clinical benefit. Under the trial’s prespecified statistical design, a statistically significant improvement in OS would establish a positive trial outcome, even if the PFS dual primary end point was not met. “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,” Türeci said.¹ “As immune-mediated anti-tumor 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.”

What is the AHEAD-MERIT trial design?

AHEAD-MERIT is an open-label, controlled, multisite, 2-arm phase 2/3 trial of BNT113 in combination with pembrolizumab compared with pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16-positive HNSCC expressing PD-L1 with a combined positive score of 1 or higher.² The trial includes an initial, non-randomized safety run-in phase (Part A) to confirm the safety and tolerability of BNT113 plus pembrolizumab at the selected dose range, and a randomized part (Part B) to generate pivotal efficacy and safety data vs pembrolizumab monotherapy. Patients are treated for up to approximately 24 months. Part B has 2 dual primary end points, PFS and OS; secondary end points include safety, objective response rate, and duration of response.

What is BNT113, and what is the context in HPV16-positive HNSCC?

BNT113, also known as tenumomeran/raplemomeran or “tenu-ra,” is an investigational mRNA cancer immunotherapy encoding the E6 and E7 proteins of HPV16 that are frequently found in HPV16-positive solid tumors. The approach is designed to induce HPV16-specific antitumor immune responses to enhance clinical responses in patients receiving standard-of-care checkpoint inhibitor treatment.

BNT113 received FDA fast track designation in January 2026.³ HNSCC is the seventh most common cancer type worldwide, with increasing global incidence driven mainly by a rise in HPV16-related oropharyngeal tumors; about one-third of HNSCC cases are HPV positive, of which approximately 90% of oropharyngeal cancers are driven by HPV16. Despite the distinct characteristics of HPV-positive tumors, there are currently no HPV-targeted treatments approved, and many patients with HPV16-positive HNSCC experience disease progression on current standard-of-care treatments, underscoring the continued need for novel HPV-targeted options.

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 SE. October 13, 2026. Accessed October 13, 2026. https://tinyurl.com/3f92hf6j
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 September 21, 2026. Accessed October 13, 2026. https://tinyurl.com/3jb8w6he
3. 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 October 13, 2026. https://tinyurl.com/bdfc8k6x