A Phase 1/2a, Open-label, Dose-finding Trial to Evaluate Safety, Immunogenicity, and Anti-tumor Activity of VB10.16 and Pembrolizumab in Patients with Unresectable Recurrent or Metastatic HPV16-positive Head-Neck Squamous Cell Carcinoma
This is a multi-center study in patients with un-resectable Recurrent or Metastatic HPV16-positive oropharyngeal Head and Neck Squamous Cell Carcinoma (HNSCC). The trial is designed to investigate VB10.16, an investigational therapeutic DNA vaccine in combination with another medicine, pembrolizumab, which is the standard of care for patients with previously untreated metastatic or resectable recurrent PD-L1 positive HNSCC. The study is divided in 2 parts: a phase 1, dose escalation part, testing 3 different doses of VB10.16 in combination with a standard fixed dose of pembrolizumab. The goal of this part is to evaluate the safety and tolerability of the combined treatment and to decide on the dose of VB10.16 to be used in the second part of the trial. In the second part of the trial, a phase 2a, dose expansion part, participants will receive either the highest safe dose of VB10.16 from part 1 or the 3 mg dose both in combination with pembrolizumab. The dose given to each participant will be decided in random. The trial is designed to define the optimal dose of VB10.16 in combination with pembrolizumab for future clinical studies based on the safety, tolerability and anti-tumor effect data generated.
‣ GENERAL REQUIREMENTS
• ≥18 years of age (or as per national legal age of trial consent, whichever is higher) at date of signing the informed consent form (ICF)
• Histologically or cytologically confirmed R/M HNSCC, located in the oropharynx, considered incurable by local therapy and eligible for monotherapy with pembrolizumab
• HPV16 positivity of R/M oropharyngeal HNSCC confirmed by designated central laboratory
• PD-L1 positivity (CPS ≥1) using the validated PD-L1 IHC 22C3 pharmDx (DAKO) assay.
• Primary tumor location in the oropharynx.
• At least 1 measurable lesion per RECIST 1.1
• ORGAN FUNCTION
• Overall function:
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
• Hematological function:
• Platelets ≥100 × 10\^9/L (100,000/µL)
• Neutrophils (absolute neutrophil count \[ANC\]) ≥1.5 × 10\^9/L (1,500/µL)
⁃ Hemoglobin ≥5.6 mmol/L (9.0 g/dL)
⁃ Hepatic and hemostatic function:
⁃ Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome, then direct BILI ≤2 × ULN) or direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN.
⁃ Aspartate transaminase (AST) ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
⁃ Alanine transaminase (ALT) ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
⁃ Alkaline phosphatase ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
⁃ International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case PT and partial thromboplastin time (PTT)/activated PTT (aPTT) must be within therapeutic range of intended use of anticoagulants.
⁃ Renal function:
⁃ Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m\^2 using the Cockroft-Gault formula
⁃ OTHER TRIAL REQUIREMENTS
⁃ Female patients of childbearing potential: negative serum pregnancy test (≤72 hours)
⁃ Female patients of childbearing potential must agree to use highly effective contraception throughout the trial (14 days prior to initiation of treatment for oral contraception), and for at least 120 days (according to the current version of the IB for pembrolizumab) after the last dose of pembrolizumab and up to 6 months after the last dose of VB10.16, whichever comes last.
⁃ Male patients must agree to use male condoms during intercourse throughout the trial, and up to 3 months after the last dose of VB10.16, and must refrain from sperm donation in the same period.
⁃ Patients capable of giving informed consent must provide signed and dated written informed consent prior to initiation of any study-related procedures.