Personalized Immunotherapy in Patients With Recurrent /Metastatic SCCHN That Have Progressed on Prior Immunotherapy

Inclusion Criteria

• Recurrent and/or Metastatic squamous cell carcinoma of the head and neck that is not amenable to therapy with curative intent. Patients who refuse salvage surgery or radiation for recurrence are potentially eligible.
• Failure of prior immunotherapy as defined as:
• Progression of disease on anti-PD-1 mAb or anti-PD-L1 mAb treatment in the R/M setting.
• Both patients that have received platinum based chemotherapy prior or have not yet received platinum based chemotherapy are eligible.
• Patients cannot have received more than 3 total lines of prior systemic therapy in the recurrent/metastatic setting.
• ECOG performance status of 0-1
• Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1.
• Provide adequate tissue (core or incisional/excisional biopsy) prior to starting study for analysis for gene expression of LAG3 and CTLA4 per OmniSeq Immune Report Card. FNA is not adequate. Archival tissue can only be used if it was obtained in the recurrent/metastatic setting and there has been no subsequent cancer treatment after that tissue was obtained.
• Life expectancy of at least 12 weeks based on investigator estimate.
• Age ≥ 18 years old
• LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test) within 6 months from first study drug administration
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤2.5 x institutional ULN
• creatinine ≤ institutional ULN

OR

• glomerular filtration rate ≥40 mL/min/1.73 m2 for patients with creatinine levels. (GFR) above institutional normal.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 1 days 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 1 methods of birth control or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Women 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 7 months after the last dose of study therapy.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• SCC of salivary gland origin or cutaneous SCC of the head and neck. HNSCC of unknown origin ARE eligible.
• Patients who received Ipilimumab or Relatlimab in the recurrent/metastatic setting will be excluded.
• Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 2 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (equivalent of >10 mg of prednisone) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody, chemotherapy, or targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier (alopecia is an exception). Note: Subjects with ≤ Grade 2 neuropathy, ototoxicity, hypothyroidism or hyperthyroidism, are an exception to this criterion and qualify for the study.
• History of other malignancy within 3 years with the exception of prior HNSCC, adequately treated basal cell or squamous cell skin cancer, or carcinoma of the cervix.
• Has an active autoimmune disease requiring systemic immunosuppressive treatment within the past 3 months. Subjec