Diclofenac for the Treatment of Patients With Metastatic Non-small Cell Lung Cancer on Single Agent Immunotherapy

Inclusion Criteria:

* Capable of signing informed consent
* Age ≥ 18 years at time of study entry
* Stage III or IV pathologically proven NSCLC with advanced or metastatic disease, currently on treatment with an Food and Drug Administration (FDA) approved single agent monoclonal antibody inhibiting the PD(L)-1 pathway (pembrolizumab, atezolizumab, nivolumab, or cemiplimab) for a minimum of 12 weeks

  * May include frontline single agent immune checkpoint inhibitors (ICI), maintenance single agent ICI after chemo-ICI, or subsequent line therapy
* Radiographic evidence of clinical progression as determined by the treating physician, not warranting immediate change of therapy. Progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria is not required. This can include mixed response, will need at least one growing lesion. Exposure to PD1 inhibitor for at least 12 weeks will minimize the risk of pseudo-progression
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Life expectancy of ≥ 26 weeks
* Absolute neutrophil count (ANC) ≥ 1,000 cell/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 gm/dL
* Creatinine clearance ≥ 45 ml/ml
* Bilirubin ≤ 1.5 x institutional upper limit of normal

  * Bilirubin must be ≤ 3 x institutional upper limit of normal in patients with documented Gilbert's syndrome
* Serum glutamic oxaloacetic transaminase (SGOT) / serum gluatmic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal
* Ability to take oral medications
* Willingness and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria:

* Concurrent enrollment in another clinical study, unless it is non-therapeutic
* Prophylactic or therapeutic anticoagulation therapy including but not limited to: warfarin, heparin, low molecular weight heparin, or direct oral anticoagulants, including: dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa)
* Treatment within the previous 6 weeks or planned initiation of bevacizumab
* Abnormal markers of coagulation as measured by international normalized ratio (INR) \> 2
* Contraindication for NSAID therapy including: chronic aspirin therapy for coronary artery disease (CAD), cerebrovascular accident (CVA), or other indication, uncontrolled gastrointestinal ulcerative disease, known bleeding diathesis, known allergy or hypersensitivity to NSAIDS, advanced renal disease, uncontrolled hypertension, known seizure disorder or others
* Female of childbearing potential unwilling or unable to use 2 methods of contraception, detailed in protocol
* Uncontrolled intercurrent illness
* History of another primary malignancy with exceptions noted in protocol
* History of active primary immunodeficiency or active infection including tuberculosis, hepatitis B, hepatitis C
* Current or prior use of immunosuppressive medication within 14 days before the first dose of diclofenac. There are exceptions to this criterion
* Receipt of live attenuated vaccine within 30 days prior to the first dose of study medications
* Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements