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Investigating a new cancer vaccine combined with pembrolizumab for HPV16 positive head and neck cancer

An Open-label Phase II/III Randomized Trial of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Monotherapy as a First Line Therapy in Patients With Unresectable Recurrent, or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Which is Positive for Human Papilloma Virus 16 (HPV16+) and Expresses PD-L1

Phase2; Phase3 Interventional BioNTech SE · NCT04534205

This study is testing a new cancer vaccine combined with pembrolizumab to see if it helps people with HPV16 positive head and neck cancer more than pembrolizumab alone.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment350 (estimated)
Ages18 Years and up
SexAll
SponsorBioNTech SE Industry-sponsored
Drugs / interventionsdenosumab, prednisone, pembrolizumab
Locations193 sites (Los Angeles, California and 192 other locations)
Trial IDNCT04534205 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, tolerability, and therapeutic effects of BNT113, a cancer vaccine, in combination with pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for Human Papilloma Virus 16 and expresses PD-L1. The trial consists of two parts: an initial non-randomized safety run-in phase to confirm the safety of the combination treatment, followed by a randomized phase to assess the efficacy and safety of the combination versus monotherapy. Patients will be monitored for treatment responses and side effects throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are patients with unresectable recurrent or metastatic HPV16 positive HNSCC expressing PD-L1 with a combined positive score of 1 or higher.

Not a fit: Patients with head and neck cancers that are not HPV16 positive or do not express PD-L1 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat head and neck cancers.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, suggesting potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Patients must sign the written pre-screening informed consent form (ICF) before any pre-screening procedures.
* Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC that is considered incurable by local therapies.
* Patients who have a tumor that expresses PD-L1 \[CPS ≥1\] as determined by the European Conformity (CE)-marked/Food and Drug Administration-approved CDx PD-L1 immunohistochemistry 22C3 pharmDx performed according to the manufacturer's instructions for use.
* Patients must not have had prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 180 days prior to randomization, if given as part of multimodal treatment for locally advanced disease, is allowed.
* Patients who have measurable disease based on RECIST 1.1 as determined by the site and confirmed by BICR. Tumor lesions situated in a previously irradiated area may be considered measurable, if progression has been demonstrated in such lesions disease by RECIST 1.1.
* All patients must provide a tumor tissue sample (formalin fixed paraffin embedded \[FFPE\] blocks or both slides and curls) from archival tissue. Alternatively, a fresh biopsy sample could be provided if a biopsy sample is performed as part of the patient's standard clinical practice before the first dose of trial treatment. The sample should be preferably derived from a current site of metastatic or recurrent disease. Otherwise, a sample from the primary tumor can be submitted.

Key Exclusion Criteria:

Medical conditions:

* Patients present primary tumor site of nasopharynx (any histology).
* Patients with another primary malignancy that has not been in complete remission for at least 2 years, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, non-invasive basal or non-invasive squamous cell skin cancer, localized prostate cancer, non-invasive superficial bladder cancer or breast ductal carcinoma in situ).

Prior/concomitant therapy:

* Patients who have received or currently receive the following therapy/medication:

  1. Chronic systemic immunosuppressive treatment including corticosteroid treatment (prednisone \>10 mg daily orally \[PO\] or intravenously \[IV\], or equivalent) in the 7 days prior to the first dose of trial treatment.
  2. Prior treatment with other immune-modulating agents that was (a) within fewer than 4 weeks (28 days) or five half-lives of the agent (whichever is longer) prior to the first dose of BNT113, or (b) associated with immune-mediated AEs that have not resolved prior to the first dose of BNT113 or that pose an additional risk of on-trial complications, per investigator's assessment, or c) associated with toxicity that resulted in discontinuation of the immune-modulating agent and that poses an additional risk of on-trial complications, per investigator's assessment.
  3. Prior treatment with live attenuated vaccines within 4 weeks before the first dose of BNT113.
  4. Prior treatment with an investigational drug (including investigational vaccines) within 4 weeks or five half-lives of the agent (whichever is longer) before the planned first dose of BNT113.
  5. Ongoing treatment with therapeutic PO or IV antibiotics. Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) may be enrolled.
* Prior treatment with anti-cancer immunomodulating agents, such as blockers of programmed death receptor-1 (PD-1), PD-L1, tumor necrosis factor receptor superfamily member 9 (TNRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines, cytokine treatments, or any investigational agent within 4 weeks or five half-lives of the agent (whichever is longer) before the first dose of BNT113.
* Treatment with non-systemic anti-cancer therapy (e.g., radiotherapy or surgery) within 2 weeks prior to randomization. Note: Prior treatment with bone resorptive therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid) and denosumab, is allowed.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Los Angeles, California and 192 other locations

+143 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Unresectable Head and Neck Squamous Cell CarcinomaMetastatic Head and Neck CancerRecurrent Head and Neck CancerCancer vaccineRNA vaccineHNSCCBNT113Pembrolizumab
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.