Safety and Efficacy of VB10.16 and Pembrolizumab in Patients with Head-Neck Squamous Cell Carcinoma

Exclusion Criteria56

• HNSCC DISEASE
• Has disease that is suitable for local therapy with curative intent
• Has progressive disease ≤6 months after completion of curatively intended concurrent chemoradiotherapy for locoregionally advanced R/M oropharyngeal HNSCC
• Primary tumor site of the oral cavity, hypopharynx, larynx or nasopharynx (any histology)
• Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator
• PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS
• Has received prior palliative radiotherapy within 2 weeks of start of trial treatment or has a prior history of radiation pneumonitis
• Any prior investigational or approved systemic antineoplastic drug or invasive medical device (including ICIs), either as monotherapy or as part of a combination regimen administered in the R/M HNSCC setting
• Prior solid organ or tissue transplantation (except corneal transplant)
• Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
• Prior chimeric antigen receptor T (CAR-T) cell therapy
• Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecule with similar mechanism of action) that engages T-cells
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention
• Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to VB10.16 treatment start
• Prior administration with a therapeutic HPV16 vaccine
• Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α) blockers for any concurrent condition
• Chronic administration of systemic corticosteroids: prednisone \>10 mg daily (or dose equivalent)
• Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or plasma components ≤2 weeks prior to VB10.16 treatment start
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
• Has received prior surgery within 4 weeks prior to treatment
• Any planned major surgery
• PRIOR OR CONCURRENT MORBIDITY
• Malignancy:
• Past or current malignancy other than inclusion diagnosis, except for:
• Malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for at least 3 years before screening and felt to be at low risk for recurrence by the treating physician
• Adequately treated breast ductal carcinoma in situ without evidence of disease
• Adequately treated cervical carcinoma in situ, without evidence of disease
• Adequately treated non-melanoma skin cancer without evidence of disease
• Adequately treated superficial or in situ carcinoma of the bladder without evidence of disease
• Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Hepatic and hemostatic function:
• Any current bleeding disorder, active bleeding, or bleeding diathesis
• Cardiovascular function:
• Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia
• History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), despite optimal medical management
• Any other significant cardiac disease(s) that, in the opinion of the investigator, is/are clinically significant and/or unacceptable
• Pulmonary function:
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• Immune system and infectious diseases:
• Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection
• Any active, acute, or chronic infection that is uncontrolled and/or requires systemic treatment
• Known allergies, sensitivity, or intolerance to VB10.16 (active substance or to any of the excipients), pembrolizumab (active substance or to any of the excipients), or aminoglycosides (especially kanamycin).
• Central nervous system (CNS) function:
• Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or stroke
• Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment
• New (≤6 months), progressive and/or symptomatic brain metastases
• OTHER
• Is currently participating in or has participated in a trial of an investigational agent or device in the R/M setting.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the trial or interfere with the patient's participation for the full duration of the trial, such that it is not in the best interest of the patient to participate, in the opinion of the treating investigator
• Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the trial
• Has a concomitant medical condition requiring receipt of a therapeutic anticoagulant that, in the opinion of the treating physician, would contraindicate administration of VB10.16 and tumor biopsies
• Female patients who are pregnant or breastfeeding