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
- Conditions
- nresectable recurrent, or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) which is positive for human papilloma virus 16 (HPV16+) and expresses PD-L1MedDRA version: 26.1Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001400-41-SE
- Lead Sponsor
- BioNTech SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 285
1. Patients must sign the written ICF before any screening procedure.
Informed consent must be documented before any trial-specific
screening procedure is performed.
2. Patients must be aged =18 years on the date of signing the informed
consent.
3. Patients must be willing and able to comply with scheduled visits,
treatment schedule, laboratory tests, and other requirements of the trial.
4. Patients who present histologically confirmed recurrent or metastatic
HPV16+ HNSCC that is considered incurable by local therapies.
5. Patients who have a tumor that expresses PD-L1 [CPS =1] as
determined by the approved test PD-L1 IHC 22C3 pharmDx kit
performed and evaluated according to the manufacturer's specifications
and relevant regulatory approvals.
6. The eligible primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx.
7. Patients must not have had prior systemic anticancer therapy
administered in the incurable 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.
8. Patients who have measurable disease based on RECIST 1.1 as
determined by the site and confirmed by blinded independent central
review (BICR). Tumor lesions situated in a previously irradiated area
may be considered measurable if progression has been demonstrated in
such lesions by RECIST 1.1.
9. Patients have Eastern Cooperative Oncology Group (ECOG)
performance status =1.
10. Patients have adequate bone marrow function as defined by
hematological parameters described in the protocol.
11. Patients have adequate hepatic function, as defined in the protocol.
12. Patients should have adequate kidney function, assessed by the
estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m2 using
the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation.
13. Patients should be stable with adequate coagulation, as determined
by the investigator. Results should be discussed with the Medical
Monitor if:
a. international normalized ratio (INR) or prothrombin time (PT) >1.5 ×
ULN (unless on therapeutic anticoagulants with values within
therapeutic window),
b. activated partial thromboplastin time (aPTT) >1.5 × ULN (unless on
therapeutic anticoagulants with values within therapeutic window).
14. All patients must provide a tumor tissue sample (FFPE blocks or both
slides and curls) from archival tissue, or fresh biopsy if a biopsy 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. More information
about sample quality, requirements, and handling will be provided in a
laboratory manual.
15. Women of childbearing potential (WOCBP) must have a negative
serum (beta-human chorionic gonadotropin) at screening.
16. WOCBP must agree to practice at least one highly effective method
of contraception during trial, i.e., starting at screening, during the trial
and for at least 6 months after receiving the last dose of BNT113 AND for
at least 6 months after receiving the last dose of pembrolizumab.
17. WOCBP must agree not to donate eggs (ova, oocytes) for the
purposes of assisted reproduction during trial starting at screening,
during the trial and for 6 months
1. Patients are pregnant or breastfeeding.
2. Patients present primary tumor site of nasopharynx (any histology).
3. Patients with uncontrolled intercurrent illness as defined in the protocol points a/b/c/d/e/f/ g/h/I/j/k/l/m.
4. Patients with a known allergy, hypersensitivity, or intolerance to BNT113 or its excipients, or to pembrolizumab or its excipients.
5. Patients who have had a splenectomy.
6. 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.
7. Patients who have a known history (testing not required) or has a positive test at screening of any of the following:
a. Human immunodeficiency virus (HIV) 1 or 2.
b. Hepatitis B infection.
c. Hepatitis C (unless considered cured)
8. 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).
Note 1: Adjuvant hormone therapy used for breast cancer in long-term
remission is allowed.
Note 2: Any uncertainties should be discussed with the Medical Monitor.
9. 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 assessments.
10. Patients who have received or currently receive the therapy/medication as defined in the protocol points a/b/c/d/e/f.
11. Prior treatment with anti-cancer immunomodulating agents, such as
blockers of PD 1, PD-L1, tumor necrosis factor receptor superfamily
member 9 (TNFRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines,
cytokine treatments, or any investigational agent within 4 weeks or 5
half-lives of the agent (whichever is longer) before the first dose of
BNT113.
12. 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.
13. Current evidence of Common Terminology Criteria for Adverse Events
(CTCAE, version 5.0) 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.
14. Current evidence of new or growing brain or spinal metastases
during screening. Patients with known brain or spinal metastases may
be eligible if they:
a. had radiotherapy or another appropriate therapy for the brain or
spinal metastases,
b. have no neurological symptoms (excluding Grade =2 neuropathy),
c. have no evidence of clinical or radiological progression within 4 wks
before signing the informed consent,
d. do not require steroid therapy within 7 d before randomization or are
undergoing slow steroid tapering, currently at doses =10 mg and
neurologically stable.
e. spinal bone metastases are allowed unless imminent fracture or cord
compression is anticipated.
15. Patients who have previously been enro
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method