Immune Checkpoint Inhibitor (ICI)-Drug-Drug Interaction (DDI) Study

Inclusion Criteria:

* ≥ 18 years old at the time of informed consent
* Diagnosed with cancer AND initiating therapy with single agent or combination therapy that includes an immune checkpoint inhibitor (e.g., atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, relatlimab, tremelimumab)
* Ability to provide written informed consent and HIPAA authorization

Exclusion Criteria:

* Actively pregnant or breastfeeding
* Body weight less than 50 kg or a BMI \>35
* Low baseline hemoglobin, defined as \<10 g/dL

  * Note: if a prospective patient's hemoglobin returns to the normal range, they can be re-screened for trial inclusion)
* Past medical history of chronic liver disease, signs and symptom of liver disease (e.g., jaundice, ascites), or aspartate aminotransferase \>96 U/L, alanine aminotransferase \> 80 IU/L, alkaline phosphatase \>260 U/L, or total bilirubin \> 2.6 mg/dL

  * Note: if a prospective patient's liver function tests return to the normal ranges, they can be re-screened for trial inclusion)
* Past medical history of chronic kidney disease, signs and symptom of kidney disease (e.g., decreased urine output, swelling in feet and ankles), or estimated glomerular filtration rate \<45 mL/minute/1.73 m2 BSA

  * Note: if a prospective patient's kidney function returns to the normal range, they can be re-screened for trial inclusion)
* Poor performance status that makes it unlikely the patient will complete 3 cycles of immune checkpoint inhibitor (at the treating oncologist's discretion)
* Diagnosis or past medical history of autoimmune disorder, including systemic lupus erythematosus, Crohn's disease, Sjogren's syndrome, multiple sclerosis, type 1 diabetes mellitus, Behcet's disease, and ankylosing spondylitis
* History of intolerance, allergic reaction, or hypersensitivity to any of the study drugs (tizanidine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam, rosuvastatin)
* Current infection requiring medical treatment (note: if a prospective patient's infection resolves, they can be re-screened for trial inclusion)
* Concomitant treatment with systemic immunosuppressant drugs (see Appendix 3 for list)

  * Note: patients may be re-screened for trial eligibility if they discontinue any exclusionary drugs for ≥7 days prior to Study Visit 1
* Concomitant treatment with a CYP/transporter probe cocktail drug or strong inhibitors, inducers, or agents that affect the pharmacokinetics of the relevant CYP enzymes or drug transporters (see Appendix 4 for list)

  * Note: patients may be re-screened for trial eligibility if they discontinue any exclusionary drugs for ≥7 days prior to Study Visit 1
* Are unwilling/unable to avoid drugs of abuse, tobacco products or marijuana, or consuming more than 2 alcoholic drinks per day during the study
* Inability to take oral medication