Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors

Melanoma-specific inclusion criteria: • Histologically or cytologically confirmed diagnosis of cutaneous stage III melanoma according to the American Joint Committee on Cancer (AJCC) 8th edition. Patients with resectable tumors are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal metastasis or at the time of clinically detected nodal recurrence; they may belong to any of the following groups: * Primary cutaneous melanoma with clinically apparent regional lymph node metastases * Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin * Clinically detected primary cutaneous melanoma involving multiple regional nodal groups * Clinically detected nodal melanoma (if single site) arising from an unknown primary * Relapsed resectable stage III melanoma SCCHN-specific inclusion criteria: • Stage III or IVA resectable locoregionally advanced SCCHN of the oral cavity, oropharynx (with known HPV-negative or p16-negative status assessed per institution standard or centrally), hypopharynx, or larynx. Inclusion criteria applicable across cohorts: In addition to the indication-specific inclusion criteria, a patient must meet all the following general criteria to be eligible for participation in this trial: 1. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 2. Candidate for surgical resection with curative intent 3. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial. 4. Age ≥18 years on the day of signing the informed consent form 5. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. 6. Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1 7. Adequate organ function as defined below performed on screening labs obtained within 4 weeks before first dose: * Absolute neutrophil count (ANC) ≥1500/µL * Platelets ≥100 000/µL * Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Note: Criterion must be met without packed red blood cell transfusion within the prior 2 weeks. Patients can be on stable dose of erythropoietin \[≥ approximately 3 months\].) * Creatinine or measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) ≤1.5 × upper limit of normal (ULN) or ≥30 mL/min for patient with creatinine levels \>1.5 × institutional ULN * Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 × ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN * International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within the therapeutic range of intended use of anticoagulants * Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy as long as PT or PTT is within the therapeutic range of intended use of anticoagulants 8. Women of childbearing potential: Negative urine or serum pregnancy within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Women of childbearing potential: Willing to use highly effective contraception or abstain from heterosexual activity for the duration of the trial and for at least 120 days after the last dose of trial medication 10. HIV-infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: a Patients on ART must have a CD4+ T-cell count \>350 cells/mm3 at time of screening b Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to first dose of trial medication (Day 1) c Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to first dose of trial medication (Day 1) 11. Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to start of trial intervention. Note: Patients should remain on anti-viral therapy throughout trial intervention and follow local guidelines for HBV anti-viral therapy after completion of trial intervention. Hepatitis B screening tests are not required unless: * Known history of HBV infection * Mandated by local health authority. 12. Patients with a history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Patients must have completed curative antiviral therapy at least 4 weeks prior to start of trial intervention. Hepatitis C screening tests are not required unless: * Known history of HCV infection * Mandated by local health authority. Melanoma-specific exclusion criteria: * Current or prior history of uveal, mucosal, or acral melanoma * Oligometastatic stage IV melanoma * History of in-transit metastases within the last 6 months * Prior therapy targeting BRAF and/or MEK SCCHN-specific exclusion criteria: • Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma Exclusion criteria applicable across cohorts: In addition, patients meeting any of the following criteria must be excluded: 1. Currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks of the first dose of trial treatment Note: Pati