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.
- 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
- 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
- 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.
- 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
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
- 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
- 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
- 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
- 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).