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


I'm Interested

Trial ID: NCT04534205


An open-label, controlled, multi-site, interventional, 2-arm, Phase II trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing programmed cell death ligand -1 (PD-L1) with combined positive score (CPS) ≥1. This trial has two parts. Part A, an initial non-randomized Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab. Part B, the Randomized part of the trial to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the first line setting in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with CPS ≥1.

Official Title

An Open Label Phase II 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 (AHEAD-MERIT)

Stanford Investigator(s)

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   - Patients must sign the written informed consent form before any screening procedure.
   Informed consent must be documented before any trial-specific screening procedure is

   - Patients must be aged ≥18 years on the date of signing the informed consent.

   - Patients must be willing and able to comply with scheduled visits, treatment schedule,
   laboratory tests, and other requirements of the trial.

   - Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC
   that is considered incurable by local therapies.

   - Patients who have a tumor expressing PD-L1 [CPS ≥1] as determined by the Food and Drug
   Administration (FDA)-approved test PD-L1 22C3 pharmDx kit performed and evaluated
   according to the manufacturer's specifications.

   - The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and
   larynx. Patients may not have a primary tumor site of nasopharynx (any histology).

   - Patients must not have had prior systemic anticancer therapy administered in the
   recurrent or metastatic setting. Systemic therapy which was completed more than 6
   months 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 are
   considered measurable, if progression has been demonstrated in such lesions disease by
   RECIST 1.1.

   - Patients have Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

   - Patients have adequate bone marrow function.

   - Patients have adequate hepatic function.

   - Patients should have adequate kidney function, assessed by the estimated glomerular
   filtration rate ≥45 mL/min using the Chronic Kidney Disease Epidemiology Collaboration
   (CPK-EPI) equation.

   - Patients should be stable with adequate coagulation.

   - All patients must provide a tumor tissue sample (formalin fixed paraffin embedded
   (FFPE) blocks/slides) from archival tissue, or fresh biopsy if collected as part of
   patient's standard clinical practice before the first dose of trial treatment.

   - Women of childbearing potential (WOCBP) must have a negative serum (beta-human
   chorionic gonadotropin) at screening. Patients that are postmenopausal or permanently
   sterilized can be considered as not having reproductive potential.

Exclusion Criteria:

Medical conditions:

   - Patients are pregnant or breastfeeding.

   - Patients present primary tumor site of nasopharynx (any histology).

   - Patients with uncontrolled intercurrent illness, including but not limited to:

      1. Ongoing or active infection which requires systemic treatment with antibiotics or
      corticoid therapy within 14 days before the first dose of trial treatment.

      2. Symptomatic congestive heart failure (Grade III or IV as classified by the New
      York Heart Association), myocardial infarction within 3 months before screening,
      unstable angina pectoris, or cardiac arrhythmia.

      3. Arterial thrombosis or pulmonary embolism within ≤6 months before the start of
      trial treatment.

      4. Known recent history (in the past 5 years) or presence of significant pulmonary
      conditions such as uncontrolled chronic lung disease, or any evidence of
      interstitial lung disease, or active, non-infectious pneumonitis.

      5. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or
      diastolic blood pressure ≥100 mmHg, despite optimal medical management.

      6. Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T
      negative severe combined immunodeficiency [SCID]) or combined T and B cell
      immunodeficiencies (e.g., T and B negative SCID, Wiskott Aldrich syndrome, ataxia
      telangiectasia, common variable immunodeficiency).

      7. Ongoing or recent evidence (within the past year) of significant autoimmune
      disease that required treatment with systemic immunosuppressive treatments which
      may suggest risk for immune-related adverse events (AEs).

      Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related
      hypothyroidism who are in remission, or on a stable dose of thyroid-replacement
      hormone, vitiligo, or psoriasis may be included.

      8. Non-healing wound, skin ulcer (of any grade), or bone fracture.

      9. Patients with prior allogeneic stem cell or solid organ transplantation.

   10. Patients with the following risk factors for bowel perforation (e.g., history of
      acute diverticulitis or intra-abdominal abscess in the last 3 years; history of
      gastrointestinal obstruction or abdominal carcinomatosis).

   11. Patients with uncontrolled Type 1 diabetes mellitus. Note: Patients controlled on
      a stable insulin regimen are eligible.

   12. Patients with uncontrolled adrenal insufficiency.

   13. Any other disease, metabolic dysfunction, physical examination finding, and/or
      laboratory finding giving reasonable suspicion of a disease or condition that
      contraindicates the use of an investigational drug or may render the patient at
      high risk for treatment of complications.

   - Patients with a known allergy, hypersensitivity, or intolerance to BNT113 or its
   excipients, or to pembrolizumab or its excipients.

   - Patients who have had a splenectomy.

   - Patients who have had major surgery (e.g., requiring general anesthesia) within 4
   weeks before screening, or have not fully recovered from surgery, or have a surgery
   planned during the time of trial participation.

   - Patients who have a known history (testing not required) or has a positive test at
   screening of any of the following:

      1. Human immunodeficiency virus (HIV) 1 or 2.

      2. Hepatitis B (carrier or active infection).

      3. Hepatitis C (unless considered cured 5 years post curative anti-viral therapy).

   - 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).

   - Patients with any condition for which, in the opinion of the investigator,
   participation would not be in the best interest of the patient (e.g., compromise the
   well-being) or that could prevent, limit, or confound the protocol-specified

Prior/concomitant therapy:

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

      1. Chronic systemic immunosuppressive corticosteroid treatment (prednisone >5 mg
      daily orally [PO] or IV, or equivalent) during the trial. Note: Replacement
      therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or
      pituitary insufficiency) is not considered a form of systemic treatment and is

      2. Prior treatment with other immune modulating agents that was (a) within fewer
      than 4 weeks (28 days) or 5 half-lives of the agent (whichever is longer) prior
      to the first dose of BNT113, or (b) associated with immune-mediated AEs that were
      Grade ≥1 within 90 days prior to the first dose of BNT113, or (c) associated with
      toxicity that resulted in discontinuation of the immune-modulating agent.

      3. Prior treatment with other immune modulating agents for any non-cancer disease
      within 4 weeks or 5 half-lives of the agent (whichever is longer) before the
      first dose of BNT113.

      4. Prior treatment with live attenuated vaccines within 4 weeks before the first
      dose of BNT113.

      5. Prior treatment with an investigational drug (including investigational vaccines)
      within 4 weeks or 5 half-lives of the agent (whichever is longer) before the
      planned first dose of BNT113.

      6. Therapeutic PO or IV antibiotics within 14 days prior to enrollment. • Note:
      Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary
      tract infection or chronic obstructive pulmonary disease) may be enrolled.

   - Prior anti-cancer therapy in the metastatic or in the unresectable recurrent HNSCC

   - 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 before the first dose of BNT113.

   - Treatment with other anti-cancer therapy including chemotherapy, radiotherapy with
   curative intent, major surgery with curative intent or biological cancer therapy
   within 6 months prior to randomization. Adjuvant hormone therapy used for breast
   cancer in long term remission is allowed.

      - Note 1: Palliative radiotherapy and palliative surgery are allowed.

      - Note 2: Prior treatment with bone resorptive therapy, such as bisphosphonates
      (e.g., pamidronate, zoledronic acid) and denosumab, is allowed assuming that the
      patients have been on stable doses for ≥4 weeks prior to first dose of trial

Other comorbidities:

   - Current evidence of Common Terminology Criteria for Adverse Events (CTCAE, v5.0) Grade
   >1 toxicity before the start of treatment, except for hair loss and those Grade 2
   toxicities listed as permitted in other eligibility criteria. Patients with Grade 2
   neuropathy may be eligible at investigator's discretion.

   - Current evidence of new or growing brain or spinal metastases during screening.
   Patients with known brain or spinal metastases may be eligible if they:

      1. had radiotherapy or another appropriate therapy for the brain or spinal

      2. have no neurological symptoms (excluding Grade ≤2 neuropathy),

      3. have stable brain or spinal disease on the computer tomography (CT) or magnetic
      resonance imaging (MRI) scan within 4 wks before signing the informed consent,

      4. do not require steroid therapy within 7 d before randomization,

      5. spinal bone metastases are allowed, unless imminent fracture or cord compression
      is anticipated.

Other exclusions:

   - Patients who have previously been enrolled in this trial.

   - Patients with substance abuse or known medical, psychological, or social conditions
   that may interfere with the patient's participation in the trial or evaluation of the
   trial results.

   - Patients affiliated with the investigational site (e.g., a close relative of the
   investigator or dependent person, such as an employee or student of the trial site).


biological: BNT113

biological: Pembrolizumab


I'm Interested

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Elizabeth Winters

New Trial Alerts

Receive email alerts when trials open to patients.