Tailored drug combo tested for tough head and neck cancers

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. 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. 2. Failure of prior immunotherapy as defined as: 1. Progression of disease on anti-PD-1 mAb or anti-PD-L1 mAb treatment in the R/M setting. 2. Both patients that have received platinum based chemotherapy prior or have not yet received platinum based chemotherapy are eligible. 3. Patients cannot have received more than 3 total lines of prior systemic therapy in the recurrent/metastatic setting. 4. ECOG performance status of 0-1 5. Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1. 6. 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. 7. Life expectancy of at least 12 weeks based on investigator estimate. 8. Age ≥ 18 years old 9. LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test) within 6 months from first study drug administration 10. 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. 11. 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. 12. 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. 13. 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. 14. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. SCC of salivary gland origin or cutaneous SCC of the head and neck. HNSCC of unknown origin ARE eligible. 2. Patients who received Ipilimumab or Relatlimab in the recurrent/metastatic setting will be excluded. 3. 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. 4. 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. 5. 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. 6. 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. 7. Has an active autoimmune disease requiring systemic immunosuppressive treatment within the past 3 months. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. 8. Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: 1. Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent; 2. Uncontrolled angina within the 3 months prior to consent; 3. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation); 4. QTc prolongation \> 480 msec; 5. History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc.); 6. Cardiovascular disease-related requirement for daily supplemental oxygen 7. History of two or more MIs OR two or more coronary revascularization procedures 8. Subjects with history of myocarditis, regardless of etiology. 9. A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent 10. Subjects with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy). 11. Troponin T (TnT) or I (TnI) \> 2 × institutional ULN. Subjects with TnT or TnI levels between \> 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤1 x ULN. If TnT or TnI levels are \>1 to 2 × ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment based on the discretion of the PI. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \< 2 x ULN, the subject may undergo a cardiac evaluation and be considered for treatment, based on the discretion of the PI. 12. Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis. 13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 15. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 24 weeks after the last dose of trial treatment. 16. Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 17. Has active Hepatitis B or Hepatitis C 18. Has a history of a solid organ transplant.