Tenumomeran/Raplemomeran Plus Pembrolizumab Misses PFS End Point in HPV16+ HNSCC

Tenumomeran/raplemomeran (BNT113) plus pembrolizumab (Keytruda) did not significantly improve progression-free survival (PFS) vs pembrolizumab alone in the first-line treatment of patients with unresectable recurrent or metastatic, HPV16-positive, PD-L1–expressing head and neck squamous cell carcinoma (HNSCC), missing a primary end point of the phase 3 portion of the phase 2/3 AHEAD-MERIT trial (NCT04534205).¹

According to an announcement from BioNTech, the trial’s independent data monitoring committee recommended continuing the trial to assess overall survival (OS), the study’s other primary end point. Under the prespecified statistical design, significant OS improvement could establish a positive outcome despite the PFS result.

“The potential of mRNA cancer immunotherapies in combination regimens lies in their ability to induce immune responses that may translate into durable clinical benefit and, ultimately, prolonged survival of patients. While the PFS result was not statistically significant at this first analysis, the data support continued evaluation of [tenumomeran/raplemomeran] plus pembrolizumab,” Özlem Türeci, MD, cofounder and chief medical officer of BioNTech, stated in a news release. “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 previous data were reported from AHEAD-MERIT?

Findings from an exploratory analysis of the safety run-in, phase 2 portion of AHEAD-MERIT presented at the 2024 ESMO Congress showed that at the June 24, 2024, data cutoff, evaluable patients (n = 15) achieved an unconfirmed objective response rate (ORR) by blinded independent central review (BICR) of 40.0%, including 4 complete responses and 2 partial responses.² The unconfirmed disease control rate was 53.3%. Median PFS by BICR was 3.9 months (95% CI, 2.1-10.6), and median OS was 22.6 months (95% CI, 9.8-not estimable).

What is the mechanism of action of tenumomeran/raplemomeran?

The investigational mRNA cancer immunotherapy encodes the E6 and E7 proteins of HPV16, which are frequently expressed in HPV16-positive solid tumors.^1,2 It is designed to induce HPV16-specific antitumor immune responses and enhance activity when combined with checkpoint inhibitor therapy.³

BioNTech previously announced FDA fast track designation for the immunotherapy in January 2026, based on preliminary safety and efficacy findings from AHEAD-MERIT.

How was the AHEAD-MERIT trial designed?

The open-label, multicenter phase 2/3 trial included a nonrandomized safety run-in and a randomized comparison of the combination vs pembrolizumab alone.⁴

Eligible patients needed to be at least 18 years of age with histologically confirmed recurrent or metastatic HPV16-positive HNSCC considered incurable by local therapy. Tumors needed to express PD-L1 with a combined positive score of at least 1, assessed using the 22C3 pharmDx assay. Measurable disease, a tumor tissue sample, and an ECOG performance status of 0 or 1 are required.

Prior systemic anticancer treatment in the incurable recurrent or metastatic setting was prohibited. Systemic therapy for locally advanced disease was permitted if completed more than 180 days before randomization. Patients with nasopharyngeal primary tumors were excluded.

In the randomized portion of the study, patients received tenumomeran/raplemomeran plus pembrolizumab or pembrolizumab alone.

The dual primary end points of the randomized portion were PFS by BICR using RECIST 1.1 criteria and OS. Secondary end points include ORR, duration of response, investigator-assessed PFS, and safety, including treatment-emergent adverse effects (AEs) and treatment modifications associated with AEs.

What safety findings were reported previously?

In the ESMO 2024 safety run-in analysis, all patients (n = 15) experienced an any-grade treatment-emergent AE (TEAE), and 53.3% had grade 3 or higher TEAEs; the rate of any-grade and grade 3 or higher treatment-related TEAEs were 100% and 13.3%. Frequently observed AEs included pyrexia, chills, fatigue, nausea, hypothyroidism, and influenza-like illness. One fatal AE of pulmonary sepsis was considered unrelated to treatment. No TE AEs led to discontinuation of tenumomeran/raplemomeran; 1 patient discontinued pembrolizumab because of an AE.

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 13, 2026. https://www.biontech.com/us/en/home/mediaroom/news/press-releases/2026/10/BioNTech-Provides-Update-on-Phase-2-3-Clinical-Trial-for-mRNA-Cancer-Immunotherapy-Candidate-BNT113-in-Metastatic-HPV16-positive-Head-and-Neck-Cancer.html
2. BioNTech. ESMO 2024. Presentation. 2024. Accessed October 13, 2026. https://investors.biontech.de/system/files-encrypted/nasdaq_kms/assets/2024/11/22/4-58-16/ESMO%202024_BNTX%20vFINAL.pdf
3. BioNTech receives FDA fast track designation for mRNA cancer immunotherapy candidate BNT113 in HPV16+ head and neck cancer. News release. BioNTech. January 21, 2026. Accessed October 13, 2026. https://www.biontech.com/us/en/home/mediaroom/news/press-releases/2026/01/biontech-receives-fda-fast-track-designation-mrna-cancer.html
4. 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. ClinicalTrials.gov. Updated September 21, 2026. Accessed October 13, 2026. https://clinicaltrials.gov/study/NCT04534205