Brief Summary
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 dosethe amount of medication taken 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.
For Part B, an optional pre-screening phase is available for all patients where patients’ tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing prior to screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening into the main trial.
Intervention / Treatment
- Biological: BNT113
- Biological: Pembrolizumab
Inclusion Criteria:
Pre-screening phase (optional – patients can alternatively perform tumor biomarker testing as part of the main screening phase):
- Patients must sign the written pre-screening informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. form (ICF) before any pre-screening procedures.
- Patients must have histologically confirmed recurrent or metastatic HNSCC with no prior systemic anticancer therapy administered in the recurrent or metastatic (R/M) setting.
- Patients have a clinical situation at a relatively high riskthe possibility that something bad will happen of developing R/M disease.
- Patients do not meet any exclusion criteria for the main clinical trial, except for time-dependent (e.g., prior systemic treatment in the prior 6 months) or potentially reversible conditions that in the opinion of the investigator will be resolved prior to potential enrollment into the main phase.
Main trial:
- Patients must sign the written informed consent form before any screening procedure. Informed consent must be documented before any trial-specific screening procedure is performed.
- 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 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.
- The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
- 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 advancedat a late stage, far along 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.
- Patients have Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status ≤1.
- Patients have adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function as defined by hematological parameters.
- Patients have adequate hepatic function.
- Patients should have adequate kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body function, assessed by the estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m^2 using the Chronica long-lasting disease that changes slowly over time Kidney Disease Epidemiology Collaboration (CPK-EPI) equation.
- Patients should be stable with adequate coagulation, as determined by the investigator.
- All patients must provide a tumor tissuea group of cells that work together to perform a function sample (formalin fixed paraffin embedded [FFPE] blocks or both slides and curls) from archival tissue, or fresh biopsyremoval of a section of tissue to analyse for cancer cells if a biopsy is performed as part of the patient’s standard clinical practice before the first dose of trial treatment.
- Women of childbearing potential (WOCBP) must not be pregnant. WOCBP, male patients who are sexually active with WOCBP and female partners of male patients should use a highly effective method of contraception up to at least 6 months after receiving the last dose of trial treatment, and should agree not to donate eggs (ova, oocytes) or sperm.