Immunotherapy (Pembrolizumab) and A Cancer Vaccine (IO102-IO103) before and after Surgery for the Treatment of Squamous Cell Carcinoma of the Head and Neck, KIEO Trial

Inclusion Criteria

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Patients with non-bulky/non-bulky squamous cell carcinomas of the head and neck, with an indication for surgical therapy. * Surgically resectable disease – generally that is T1N1-N2B, T2-4N0-N2b stage are generally eligible (American Joint Committee on Cancer [AJCC] 7th), however exceptions can be made after approval by the principal investigator (PI) for surgically appropriate cases. * If determined per tumor board that a low-volume/non-bulky tumor of another stage is appropriate for resection (e.g. small volume T4 with a small amount of bone invasion) such tumors may also be considered for this study if recommendation in tumor board is such.
• Be appropriate candidates for resection and curative intent therapy in general.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Consent to undergo biopsy from a newly obtained core or excisional biopsy of a tumor lesion before study drug administration, and during treatment. Biopsy in case of progressive disease is optional.
• Measurable disease per RECIST 1.1.
• Known human papillomavirus (HPV) status for oropharyngeal primary tumors.
• Pre-operative scans including MRI/CT neck and, CT chest with contrast. If contrast is contraindicated, staging PET or PET-CT is acceptable although high quality / diagnostic cross-sectional imaging of the head and neck area is recommended.
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL (within 28 days of treatment initiation).
• Platelets ≥ 100,000/mcL (within 28 days of treatment initiation).
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (within 28 days of treatment initiation) without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment).
• Serum creatinine within upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 60 mL/min for subject with creatinine levels > institutional ULN (within 28 days of treatment initiation) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]). * Creatinine clearance should be calculated per institutional standard.
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN (within 28 days of treatment initiation).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 X ULN (within 28 days of treatment initiation).
• Albumin >= 2.5 mg/dL (within 28 days of treatment initiation).
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 28 days of treatment initiation).
• Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 28 days of treatment initiation).
• Female subject of childbearing potential should have a negative urine or serum pregnancy within a 28-day window prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is considered an adequate contraception method.

Exclusion Criteria

• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to treatment allocation/registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• 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 systemic anti-cancer therapy for head and neck squamous cell carcinoma (HNSCC) including investigational agents within 4 weeks of first dose of study treatment. * Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to ≤ grade 1 or baseline. Participants with ≤ grade 2 neuropathy may be eligible. Participants with endocrine-related AEs grade ≤ 2 requiring treatment or hormone replacement may be eligible. * Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug (including live coronavirus disease 2019 [COVID-19] vaccines). Administration of killed vaccines is allowed. Administration of messenger ribonucleic acid (mRNA) or peptide vaccines (e.g., for COVID-19) is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. * Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, low grade cancers that are not expected to impact life expectancy within the next 3 years and not impact interpretation of this study are allowed (e.g. , or carcinoma in situ, curative treated breast carcinoma on adjuvant hormonal therapy, prostate cancer on hormonal suppression therapy, cervical cancer in situ, transitional cell carcinoma). Importantly cancers that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants 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 study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
• Has 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), unless it is systemic steroid therapy equal or less than outlined. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection. * Note: No HIV testing is required unless mandated by local health authority.
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection specific parameters apply as outlined below: Criteria for known Hepatitis B and C positive subjects: * Hepatitis B and C screening tests are not required unless: ** Known history of hepatitis B virus (HBV) or HCV infection ** As mandated by local health authority * Hepatitis B positive subjects: ** Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. ** Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. * Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as per assessment of the treating physician. Chronic managed disorders that are not clinically active are acceptable.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis